By the first 20 years of the 20th century, professional baseball teams had been organized in every area of West Virginia. While some form of the game appears to have been played in Ceredo as early as 1859 and Fayetteville in 1862, Wheeling is baseball's unofficial birthplace in the Mountain State.

The earliest documented team was school principal C. H. Collier's founding of the Star club in Wheeling in 1865. The Wheeling Daily Register noted an intramural game of "town ball" played by the Star Club on November 11 of that year. The first recorded match game occurred on August 1, 1866, on Wheeling Island Commons, when the city's Hunkidori Base Ball Club lost 45-12 to a team from Washington, Pennsylvania. On June 30, 1869, the Baltic of Wheeling lost badly (44-0 or worse, by different accounts) at the Wheeling Fair Grounds to the undefeated Cincinnati Red Stockings, baseball's first openly all-professional team. By this time, Wheeling was home to about 20 clubs, and the Baltic were considered the best. Other clubs from the late 1860s have been documented in Martinsburg, Charles Town, Shepherdstown, Buckhannon, Weston, and Morgantown.

In 1877, the Wheeling Standards were the first baseball team to legally incorporate in the state. Professional minor league ball came to West Virginia when the Wheeling Nail Cities and then Nailers played in the Ohio State League (1887) / Tri-State League (1888-90). Notably, the 1887 team (sometimes called the Green Stockings) was integrated, with future Negro League star and hall of famer Sol White hitting .370 while playing third base. After the 1887 season, the newly named Tri-State League banned Black players from participating.

Wheeling had teams in various minor leagues from 1894 to 1902 and in the Class B Central League from 1903 through 1924. Professional baseball ended in the city after the Wheeling Stogies moved to Akron in 1934, although semi-pro ball continued. Future major leaguers Jack Glasscock, Jesse Burkett, and Ed Delahanty, transitioned from Wheeling teams to the major leagues. All but Glasscock are in the National Baseball Hall of Fame.

White semi-pro teams from Wheeling also played regular games against the great Homestead Grays of the First National Negro League. In 1933, Wheeling hosted the second, and final, game of the Second National Negro League championship between the Pittsburgh Crawfords and Chicago American Giants in an abbreviated series. Cities such as Beckley, Bluefield, Charleston, Fairmont, and Huntington also hosted traveling Negro League games.

Charleston and Huntington had teams in the second independent Tri-State League in 1894. Parkersburg was part of the minor league Ohio-West Virginia League for its one season in 1897. In various sources, Parkersburg's team was referred to as the Killers and Greeks. Soon after, star athlete Greasy Neale emerged from Parkersburg to play a key role in the Cincinnati Reds' 1919 World Series victory over the Chicago White Sox in what is remembered as the Black Sox Scandal. Neale also played a minor league season in Wheeling in 1915 and managed Clarksburg in the Middle Atlantic League in 1927-28, 1930.

Fairmont, Clarksburg, and Piedmont played in the Class D Western Pennsylvania League in 1907. West Virginia native and future major leaguer Dick Hoblitzell played for Clarksburg. The league ceased operations at the end of the year. Fairmont and Clarksburg, joined by Grafton, switched to the Class D Pennsylvania-West Virginia League in 1908-09. Parkersburg joined briefly in 1909. When the Clarksburg Bees disbanded on June 30, 1909, Parkersburg was dropped, and the league folded at the end of the year. In 1910, Fairmont, Clarksburg, Grafton, and Mannington formed the Class D West Virginia League. When the Grafton team disbanded on July 5, that league folded. Those early teams, which consisted mostly of local players, were not affiliated with major league clubs.

Minor league ball, however, was about to grow significantly in popularity. By 1920, 14 West Virginia cities and towns had spent time in professional baseball. They were Charleston, Clarksburg, Fairmont, Follansbee, Grafton, Huntington, Mannington, Martinsburg, Montgomery, Parkersburg, Piedmont, Point Pleasant, Wheeling, and Williamson. By the early 1930s, there were 11 teams, at Beckley, Bluefield, Charleston, Clarksburg, Fairmont, Huntington, Logan, Parkersburg, Welch, Wheeling, and Williamson.

In the early 1920s, future Hall of Fame members Hack Wilson and Lefty Grove played for Martinsburg of the Class D Blue Ridge League. In June 1920, Martinsburg famously traded Grove to the minor league Baltimore Orioles for $3,500, the cost of replacing its outfield fence, which had blown down during a storm. Five years later, the Orioles sold him to the Philadelphia A’s of the American League for $100,600. Martinsburg’s trade of Grove is often listed among the worst, and strangest, in baseball history. In 1934, Frank McCormick, who would become the 1940 National League Most Valuable Player, played for the Beckley Black Knights, a minor league affiliate of the Cincinnati Reds. In 1938-39, Stan Musial played for Williamson of the Class D Mountain State League. The minor league boom of the late 1940s largely bypassed West Virginia. At that time, only Charleston, Bluefield, and Welch fielded teams.

Meanwhile, in the early 20th century, coalfield baseball was a major part of life, with coal companies sponsoring their own teams, often signing good players to less-strenuous jobs in the mines. The games brought communities together with thousands in attendance and provided opportunities for both White and Black players in segregated matches. While Black players primarily played for coal and railroad companies, the independent West Virginia Negro League played one season in 1938, with teams from Glen Rodgers, Holden, Kimberly, Kyle, Omar, and Scarbro. Coalfield baseball declined after World War II as mining jobs disappeared, coal towns shrank, and social changes such as automobiles and television reduced local support for community baseball.

Charleston entered professional baseball in 1910, calling its team the Statesmen and playing at Wehrle Park on the city's East End. The Statesmen played in the Class D Virginia Valley League with Huntington, Point Pleasant-Gallipolis (Ohio), Parkersburg, Montgomery, and Ashland-Catlettsburg (Kentucky). It was the start of a busy and productive century of baseball in the capital city. After one year in the Virginia Valley League, Charleston participated in the Class D Mountain State League (1911-12) and the Class D Ohio State League (1913-16). In 1916, the city built Kanawha Park, a 3,500-seat wooden structure on the site of what later became Watt Powell Park, but spent the next 15 years without a pro team. In 1931, Charleston joined the Class C Middle Atlantic League (1931-42), a 12-city affiliation that included Beckley, Huntington, Fairmont, Clarksburg, and Wheeling.

By 1936, Charleston and Huntington were the Middle Atlantic League's lone remaining West Virginia cities. That year, Huntington's Walter Alston, a future Hall of Fame manager, led the league with 35 home runs. Huntington dropped out after the '36 season, leaving Charleston as the league's only state representative. The other West Virginia cities offering professional baseball on the eve of World War II were Bluefield, Logan, Welch, and Williamson of the Class D Mountain State League.

Beginning with construction of 5,000-seat Watt Powell Park in 1949, Charleston began moving up the baseball ladder to the Class A Central League (1949-51), Class AAA American Association (1952-60), Class A Eastern League (1962-64), and Class AAA International League (1961, 1971-83). Charleston's move to the American Association in 1952—the highest level ever for a West Virginia city—happened suddenly and unexpectedly. On June 23 of that year, the Toledo Mud Hens moved to the West Virginia capital, thereby thrusting Charleston into competition with Milwaukee, Kansas City, St. Paul, Louisville, Indianapolis, Minneapolis, and Columbus. As a member of the American Association in 1956, the Charleston Senators produced the first future hall of famer in the city's long baseball history. Jim Bunning pitched for the team for three months before going to the Detroit Tigers.

Charleston briefly had a number of players in the 1960s and 1970s who eventually made the Hall of Fame, including pitchers Jim Kaat and Tommy John. In addition, catcher Tim McCarver, who played a partial year in Charleston in 1961, was inducted into the Hall of Fame's broadcasting wing in 2012, and Tony LaRussa, who played for the Charlies in 1974, was inducted into the hall as a manager. Only three native West Virginians are members of the Hall of Fame: Jesse Burkett, George Brett, and Bill Mazeroski.

From 1971 to 1983, the Charleston Charlies were an affiliate of the Pittsburgh Pirates, Houston Astros, Texas Rangers, and Cleveland Indians. This team produced another future hall of famer: Dave Parker, remembered for his mammoth home runs during his brief stay in 1973. After three years with no baseball (1984-86), the professional game returned to Charleston in 1987 as part of the Class A South Atlantic League (1987-2020); during these years, the team was known as the Charleston Wheelers (1987-94), Charleston Alley Cats (1995-2004), and West Virginia Power (2005-20). The Wheelers produced hall of fame reliever Trevor Hoffman. He initially was a third baseman and shortstop. Charleston manager and West Virginia native Jim Lett moved the below-average hitter and fielder to the pitcher’s mound. In the major leagues, Hoffman would become the first reliever to reach the 500- and 600-save levels. He was elected to the Hall of Fame in 2018. The National League reliever of the year award is named in his honor.

On April 14, 2005, Charleston opened a new baseball facility, Appalachian Power Park (now GoMart Ballpark), to replace Watt Powell Park.

Prior to 2015, only Charleston, Bluefield, and Princeton had professional teams. Bluefield thrived as a member of the Appalachian Rookie League from 1946 to 2020 (with a one-year absence in 1956). The team had produced major-league hall of famers Cal Ripken Jr. and Eddie Murray. Nearby Princeton joined the league in 1988, its Rays offering the Bluefield Blue Jays some cross-county competition. Huntington had a rookie team, the Cubs, from 1990 to 1994. The team, a Chicago Cubs affiliate, competed against Bluefield and Princeton and others in the Appalachian League. In 2015, the West Virginia Black Bears, a Pittsburgh Pirates affiliate, began play at the newly opened Monongalia County Ballpark as a member of the short-season New York–Penn League.

A major shift in the state's baseball landscape came in February 2021 when Major League Baseball reorganized the minor leagues, ending affiliations with the West Virginia Power and two other West Virginia teams. As part of the restructuring, the Princeton WhistlePigs and Bluefield Ridge Runners joined the revamped Appalachian League, a summer collegiate league for rising college freshmen and sophomores. The Princeton franchise ceased operations following the 2023 season. The Black Bears, meanwhile, became members of the MLB Draft League, an amateur circuit for draft-eligible prospects.

At the same time, the owners of the West Virginia Power merged with the Lexington Legends franchise, allowing the Power to become the eighth member of the Atlantic League in February 2021. Later that year, in September 2021, the team rebranded as the Charleston Dirty Birds.

Professional baseball continued to expand in the state when, in November 2023, the Appalachian League announced it would return to Huntington for the first time since 1994. Beginning in the summer of 2024, the Huntington Tri-State Coal Cats started playing their home games at the newly constructed Jack Cook Field. The team folded, however, after the 2025 season due primarily to scheduling conflicts with Marshall University baseball.

College baseball has struggled to build the same popularity as its football and basketball counterparts. However, in the 20th century, West Virginia University's baseball team, established in 1892, played in postseason college tournaments in the 1950s, 1960s, 1980s, and 1990s. The program excelled in the 2010s and 2020s under coaches Randy Mazey (2013-24) and Steve Sabins (since 2025). In 2026, WVU became the first team in West Virginia history to reach the College Baseball World Series. Marshall University fielded its first team in 1896 and has won eight conference championships, including seven in eight years between 1928 and 1935. West Virginia Wesleyan also had good teams in the 1910s and 1920s, producing major leaguers Greasy Neale, Sheriff Blake, Ken Ash, and Harry Shriver. In 1964, led by Joe Niekro on the mound, West Liberty State College (now University) won the NAIA national championship. Wesleyan, West Liberty, and most other small colleges were members at some time of the West Virginia Intercollegiate Athletic Conference, founded in 1924.

Other West Virginia natives with solid Major League careers have included Dick Padden, John Menefee, Win Mercer, Wilbur Cooper, Del Gainer, Andy Seminick, Gene Freese, Chuck Stobbs, Max Butcher, Sam Jones, Lew Burdette, Paul Popovich, Steve Yeager, Toby Harrah, John Wockenfuss, John Kruk, Rick Reed, and Jedd Gyorko. Star players in the Negro Leagues with West Virginia ties included Ted Bond, Clint Thomas, Harry Kincannon, Tommy "Toots" Simpson, Lawrence Raines, and Toni Stone.