Baines was born in Easton, Maryland. He graduated in 1977 from St. Michaels High School on Maryland’s Eastern Shore where, as a senior, he batted .532 and was named a high school All-American. The White Sox made Baines the first overall selection in the 1977 amateur draft. He received a signing bonus of $32,000 – a record low for a first overall pick. The owner of the White Sox at the time, Bill Veeck, had spotted Baines playing Little League ball years before at the age of 12.

On Opening Day 1980, Baines made his MLB debut, starting as an outfielder with the Chicago White Sox. In 1982, he had 165 hits, 25 home runs and 105 runs batted in (RBIs). In 1984, baseball writer Bill James called Baines his favorite opposing player to watch, saying, “He is gorgeous, absolutely complete. I’ve seen him drop down bunts that would melt in your mouth, come up the next time and execute a hit and run that comes straight off the chalkboard. I’ve seen him hit fastballs out of the yard on a line, and I’ve seen him get under a high curve and loft it just over the fence.” Baines ended the longest game in major league history (eight hours and six minutes over 25 innings on successive evenings) with a walk-off home run against the Milwaukee Brewers’ Chuck Porter on May 8, 1984; the bat he used is currently kept at the Baseball Hall of Fame.

Baines holds the record for the most seasons by a player between 100-RBI seasons, with 14 seasons between 113 RBIs for Chicago in 1985 and 103 for Baltimore and Cleveland in 1999.

In 1986, a succession of knee problems began which gradually ended his fielding career, forcing him to become a regular designated hitter. Despite the knee ailments and the resulting lack of speed, he remained a powerful hitter, picking up 166 hits in 1988.

Midway through the 1989 season, the Texas Rangers acquired Baines, along with Fred Manrique, from the White Sox in a much-derided trade which sent Wilson Álvarez, Scott Fletcher and Sammy Sosa to Chicago. After the trade, the White Sox retired Baines’s #3 on August 20, 1989, a rare occurrence for a player who was still active in the major leagues (the number would be “un-retired” each time Baines returned to the White Sox, and he wore it as a coach).

In 1990 Baines was traded to the Oakland Athletics for minor league pitchers Scott Chiamparino and Joe Bitker, and he helped them reach the postseason only to be swept by the Cincinnati Reds in the World Series. In 1992 the Athletics returned to the playoffs, but lost to the Toronto Blue Jays in the ALCS.

Prior to the 1993 season, Baines was traded by the A’s to the Baltimore Orioles for minor league pitchers Bobby Chouinard and Allen Plaster. Baines batted .313, .294 and .299 over his first three seasons with Baltimore. He returned to the White Sox as a free agent in 1996 but was traded back to Baltimore midway through the 1997 season; he helped the Orioles reach the playoffs, losing to the Cleveland Indians in the League Championship Series.

Baines represented the Orioles in the 1999 All Star Game before being traded to the Cleveland Indians later that year. Baines was signed again for a third stint with his hometown team prior to the 2000 season. Baines was traded by Baltimore with catcher Charles Johnson to Chicago in exchange for Miguel Felix, Juan Figueroa, Brook Fordyce and Jason Lakman on July 29, 2000.

Baines’s fourth stint with the Chicago White Sox began when he was named bench coach in March 2004 under new manager Ozzie Guillén, his White Sox teammate, from 1985 to 1989 and in 1996–97. Baines served as the team’s interim manager for four games, from August 17–20, 2004, while Guillén was serving two consecutive two-game suspensions.

In 2005, as a coach for the White Sox, he earned a World Series ring when the White Sox won the 2005 World Series.

On July 20, 2008, the White Sox unveiled a bronze statue of Baines at U.S. Cellular Field prior to their game against the Kansas City Royals; it is the seventh statue featured on the park’s outfield concourse.

In August 2009 the Orioles announced that Baines would be inducted into the Orioles Hall of Fame as the 46th member. In his seven seasons with the Orioles he batted .301, had 107 home runs, and 378 RBIs as their designated hitter.

Baines had been eligible for the National Baseball Hall of Fame beginning with the 2007 election. While 75% of the vote is needed for induction, he never received greater than 6.1% (which he received in 2010). On January 5, 2011, Baines received just 28 votes (4.8%) in the 2011 Hall of Fame election, dropping him off all future writers’ Hall of Fame ballots by receiving less than 5.0% of the vote.

On December 9, 2018, Baines and Lee Smith were elected to the National Baseball Hall of Fame Class of 2019 via the Today’s Game Era ballot, a voting panel of 16 consisting of six players, one manager, six executives, and three journalists. Many baseball writers and fans expressed shock that a player who peaked at 6.1% of votes on the regular ballot and was eliminated after only five years was allowed in through the Today’s Game Committee. Baines was voted into the Hall of Fame by his peers: he played against five of the six players on the committee, while a sixth served as manager against him. Four executives on the panel were in management while Baines was a player and his former manager and team owner also were on the committee. He and five other players were inducted into the Hall of Fame on July 21 before a crowd of 55,000, including 53 previous inductees.