Joe received little formal schooling. Due to the transient lifestyle of coal miners, his family moved frequently during his childhood. The McGinnitys moved to Gallatin County in 1878. Two days after the birth of their seventh child, Peter died in an accident. At the age of eight, Joe and his older brothers went to work in the mines to support their family. In 1880, the family moved to Springfield, Illinois, where Joe and his brothers worked for the Springfield Coal Company. They moved to Decatur, Illinois less than six months later, continuing to mine coal, while their mother cleaned houses.

While living in Decatur, McGinnity began playing baseball with other coal miners in their leisure time. The owner of the Decatur Coal Company founded the Decatur Baseball Association in 1886. An outfielder, McGinnity substituted for his team’s pitcher in an 1888 game, which he won. He continued to pitch from that point on. He pitched for semi-professional teams based in Decatur in 1888 and 1889. His family headed west, stopping in the Indian Territory on their way to Montana, where Hannah’s sister struck gold in their coal mine. McGinnity and his brothers worked in a coal mine in Krebs. There, he met his future wife, Mary Redpath, the oldest daughter of a fellow coal miner. McGinnity also played baseball for the local team. He increased baseball’s popularity in the area, and was later referred to as “the father of Oklahoma baseball” by a sportswriter for The Oklahoman, as he organized, managed, and pitched for teams in Krebs. One of these teams began traveling to other towns along the Missouri–Kansas–Texas Railroad to play against their local teams. He also pitched for teams in neighboring towns.

John McCloskey, the manager of the minor league baseball Montgomery Colts of the Class-B Southern League, heard about McGinnity’s pitching. McCloskey signed McGinnity, who made his professional debut with the Colts in 1893. McCloskey habitually baited umpires during games, a trait which McGinnity learned. The league folded as a result of financial troubles related to the Panic of 1893. Jimmie Manning, manager of the Southern League franchise in Savannah, Georgia, became manager of the Kansas City Blues of the Class-A Western League for the 1894 season, and signed McGinnity to pitch for the Blues. Combined for Montgomery and Kansas City, McGinnity had a 21–29 win–loss record, while walking more batters than he could strikeout, and allowing more than a hit per inning pitched. According to a Western League umpire, catcher Tim Donahue tipped McGinnity’s pitches to opposing batters due to a personal feud. As McGinnity continued to struggle for Kansas City, he requested his release in June.

After the 1899 season, the NL voted to contract four teams, which included the Orioles. Hanlon assigned McGinnity to Brooklyn, now known as the “Superbas”. McGinnity posted a 28–8 record for Brooklyn in the 1900 season. His 28 wins and 343 innings pitched led the league, as the Dodgers won the NL pennant. McGinnity also pitched two complete games in the Chronicle-Telegraph Cup, as the Superbas defeated the Pittsburgh Pirates. Rather than draw straws to decide who would keep the trophy, the team voted to award it to McGinnity.

Fighting continued to erupt in games McGraw managed. During a brawl that erupted during a game against the Detroit Tigers on August 21, 1901, McGinnity spat on umpire Tom Connolly. McGinnity was arrested for the incident and permanently suspended by AL president Ban Johnson, who wanted there to be no fighting in AL games. Johnson later cut the suspension down to 12 days after McGinnity apologized. McGinnity compiled a 26–20 record for the 1901 Orioles, and his 48 games, 39 complete games, and 382 innings pitched led the AL.

McGinnity began the 1902 season with the Orioles. However, the franchise began to fall into significant debt. Joe Kelley, star player for the Orioles and son-in-law of part-owner John Mahon, reported that the team owed as much as $12,000 ($354,600 in current dollar terms). Unable to afford that debt, Mahon purchased shares of the team from Kelley and player-manager John McGraw. With this, Mahon became the majority shareholder. On July 17, 1902, Mahon sold his interest in the Orioles to Andrew Freedman, principal owner of the Giants, and John T. Brush, principal owner of the Cincinnati Reds, also of the NL. That day, Freedman and Brush released McGinnity, McGraw, Kelley, Roger Bresnahan, Jack Cronin, Cy Seymour, and Dan McGann from their Oriole contracts. Brush then signed Kelley and Seymour to the Reds, while Freedman signed McGinnity, Bresnahan, Cronin, and McGann, joining McGraw, his new player-manager, on the Giants. McGinnity attempted to contact Johnson that night, offering to stay with the Orioles if he could receive Johnson’s personal assurance that he was welcome to stay. McGinnity did not hear back from Johnson, who had left his phone off the hook that night to avoid being contacted, and joined his teammates with the Giants.

With the Giants for the 1903 season, McGinnity won 31 games. He also set MLB records with 48 games started and 434 innings pitched, which remain NL records today. Jack Chesbro, pitching for the New York Highlanders of the American League during the 1904 season, set the current MLB records with 55 games started and 454 ⁄3 innings. In 1903, McGinnity started both games of a doubleheader on numerous occasions. He performed this feat three times in a single month, winning all six games. On the final instance, The New York Times reported “he seemed fresh enough to tackle the visitors for a third contest if that were necessary”. He pitched over 100 innings in the month of August. Wins by McGinnity and fellow pitcher Christy Mathewson accounted for 73% of the Giants’ winning games in 1903, setting an MLB record for a pitching tandem. After the season, McGinnity and some of his teammates threatened to quit the Giants, accusing Brush, now the Giants owner, of going back on a promise to pay the team a monetary bonus for having finished among the top three teams in the NL, as well as a share of the gate receipts from exhibition games, for which they were paid $56.35 ($1,603 in current dollar terms), though Brush allegedly had made over $200,000 ($5,691,111 in current dollar terms). McGinnity claimed that he would pitch in the California League, as he had received a salary offer for “$1,000 ($28,456 in current dollar terms) more than [he] got in New York”. Jack Warner eventually joined McGinnity in publicly threatening to quit.

McGinnity set an MLB record during the 1904 season, recording his tenth win in 21 team games on May 21, the fewest team games for a pitcher to reach the mark. In 1904, McGinnity had a 35–8 record, leading the NL in games (51), innings pitched (408), shutouts (9), saves (5), and his career-best 1.61 ERA. With the Giants competing for the pennant, McGinnity again won both games in a doubleheader three times in a matter of weeks. Aided by McGinnity, the Giants again won the NL pennant. However, they did not compete in the 1904 World Series as Brush and McGraw refused to face the AL champion Boston Pilgrims, following their altercations with Johnson. After the 1904 season, McGinnity attempted to hold out from the Giants when Brush refused to allow McGinnity to play winter baseball with a team in the Southern United States.

McGinnity won 21 games in the 1905 season, as the Giants won the NL pennant. This year, the Giants participated in the 1905 World Series, against the AL champion Philadelphia Athletics. McGinnity started Games Two and Four of the five game series against the Athletics, winning one and losing one, while Mathewson pitched and won the other three. All five games, including the game McGinnity lost to Chief Bender, were shutouts. In 1906, McGinnity again led the NL in wins, with 27. This came in spite of a suspension McGinnity served for fighting Pirates catcher Heinie Peitz, which NL president Harry Pulliam described as “attempting to make the ball park a slaughterhouse.” The Mayor of Pittsburgh, who attended the game, insisted that McGinnity be arrested.

In the 1907 season, McGinnity finished with an 18–18 record with a 3.16 ERA, allowing more than a hit per inning for the first time since the 1901 season. He missed the beginning of the 1908 season with a severe fever. In June 1908, Brush put McGinnity on waivers, hoping another owner would relieve him of McGinnity’s $5,000 salary ($142,278 in current dollar terms). He tried to waive McGinnity again in August, but both times McGinnity went unclaimed. Despite this, McGinnity reverted to his old form: from August 22 through the end of the season, McGinnity had an 11–7 record, five shutouts, a 2.27 ERA, and an NL-leading five saves. The Giants released McGinnity on February 27, 1909, when McGinnity decided to pay for his own release.

McGinnity purchased the Newark Indians of the Class-A Eastern League (EL) for $50,000 ($1,422,778 in current dollar terms) in 1909 from Frank J. Farrell. The press reported that McGinnity would operate the team as a farm team of the Giants, though he denied these reports. When McGinnity could not retain manager Harry Wolverton, he stepped in as player-manager for the Indians. That season, he had a 29–16 record. His 422 innings pitched and 11 shutouts set EL single-season records. He also won both games of doubleheaders on August 27, 1909, and July 23, 1912.

McGinnity played for and managed the Indians through 1912. The Indians finished second in the EL in 1909 and 1910. McGinnity sold his interests in the Indians to Ebbets and Ed McKeever and purchased the Tacoma Tigers of the Class-B Northwestern League for $8,500 ($225,191 in current dollar terms), spending another $50,000 ($1,324,655 in current dollar terms) on the franchise in renovating the stadium. He served as player-manager of the Tigers at the start of the 1913 season, but stepped down as manager, hiring Russ Hall to serve as manager in June. McGinnity sold stock in the team in 1915 in order to afford operating expenses. He also briefly played for the Venice Tigers of the Class-A Pacific Coast League in 1914.

McGinnity sold the Tigers and purchased the Butte Miners of the Northwestern League in 1916, serving as player-manager and bringing with him several players from Tacoma. In June 1917, he sold his stock in the team and secured his release. He played for the Great Falls Electrics of the Northwestern League for the remainder of the 1917 season. He later became the manager of the A. E. Staley factory baseball team.

McGinnity served as player-manager of the Danville Veterans of the Class-B Illinois–Indiana–Iowa League in the 1922 season and Dubuque Climbers of the Class-D Mississippi Valley League during the 1923 season. With Dubuque, McGinnity won 15 games at age 52. One of those wins was a shutout, pitched in a record one hour and seven minutes. Two years later, he returned to play for Dubuque and the Springfield Senators of the Illinois–Indiana–Iowa League during the 1925 season. He pitched in his final professional game on July 28, 1925, after participating in an old-timers game earlier in the day.

While working with Williams College’s baseball team in 1929, McGinnity became ill. He had surgery to remove tumors from his bladder, and was said to be in critical condition. After the surgery, he was quoted as saying “it’s the ninth inning, and I guess they’re going to get me out.” He died November 14, 1929 in Brooklyn, New York, at the home of his daughter. He was interred in McAlester.

After failing to receive the necessary votes from the Baseball Writers’ Association of America for entry in the National Baseball Hall of Fame on seven occasions, McGinnity was posthumously elected to the Hall of Fame by the Veterans Committee in 1946. He was also inducted into the Quad City Sports Hall of Fame in 1988.

In a 1976 article in Esquire magazine, sportswriter Harry Stein published an “All Time All-Star Argument Starter”, consisting of five ethnic baseball teams. Though Stein chose McGinnity as the right-handed pitcher for the Irish team, the team was omitted from the article due to space limitations. The Irish team was included in The Book of Lists, published the following year. Lawrence Ritter and Donald Honig included McGinnity in their 1981 book, The 100 Greatest Baseball Players of All Time. The Chicago Tribune included McGinnity in its all-time Illinois team in 1990. In his 2001 book The New Bill James Historical Baseball Abstract, Bill James ranked McGinnity as the 41st greatest pitcher of all-time.