By the first 20 years of the 20th century, professional baseball teams had been organized in every area of West Virginia. While variations of modern baseball likely were played in present West Virginia prior to the Civil War, the earliest documented team was Wheeling, which played its first game in August 1866 on Wheeling Island Commons as the Hunkidori Base Ball Club, losing 45-12 to a team from Washington, Pennsylvania. The Wheeling Nail Cities and then Nailers were the only West Virginia entries in both the Ohio State League in 1887 and the original Tri-State League, from 1888 to 1890. Future major leaguers Jesse Burkett and Jack Glasscock emerged from Wheeling’s sandlots. Wheeling later had teams in various other 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.

White semi-pro teams from Wheeling also hosted regular games against the great Homestead Grays that belonged to 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 both had teams in the second Tri-State League in 1894. Parkersburg was part of the minor Ohio-West Virginia League for its one season in 1897, the only Mountain State team to participate. In various sources, Parkersburg's team was referred to as both 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. When the league folded a year later, Fairmont and Clarksburg switched to the Class D Pennsylvania-West Virginia League. Mannington spent less than half a season in professional ball, aligning with Fairmont, Clarksburg, and Grafton to form the Class D West Virginia League in 1910. When the Grafton team disbanded on July 5, the league folded. Those early teams, which consisted mostly of local players, were not associated with the major leagues.

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.

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, 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 of four future Hall of Fame players 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.

By 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 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 playing at the new Monongalia County Ballpark as a member of the short-season New York-Penn League. In February 2021, Major League Baseball reorganized its minor league franchises, eliminating affiliations with the Power and two other West Virginia teams. The Princeton WhistlePigs and Bluefield Ridge Runners became part of the revamped Appalachian League for rising freshmen and sophomore college players; Princeton's team ceased operations after the 2023 season. The Black Bears are part of the MLB Draft League, an amateur league for draft-eligible prospects.

In February 2021 the owners of the West Virginia Power merged with the Lexington Legends ballclub, and the Power became the eighth member of the Atlantic League. In September 2021, the Power changed its name to the Charleston Dirty Birds. In November 2023, the Appalachian League announced that minor league baseball would return to Huntington for the first time since 1994. Beginning in summer 2024, the Huntington Tri-State Coal Cats began playing home games at the newly built Jack Cook Field.

In the 20th century, West Virginia University's baseball team 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.

Other West Virginia natives who have had solid Major League careers include Dick Padden, John Menefee, Win Mercer, Dick Hoblitzell, Wilbur Cooper, Del Gainer, Sheriff Blake, Any 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 League with West Virginia ties included Ted Bond, Clint Thomas, Harry Kincannon, Lawrence Raines, and Toni Stone.