Originally signed by the Philadelphia Phillies in 1978, Bell was selected by the Toronto Blue Jays in the 1980 Rule 5 draft. Bell was discovered in the Dominican Republic by Blue Jays scout Epy Guerrero. His first season as a regular was in 1984, when he teamed with Lloyd Moseby and Jesse Barfield to form a successful outfield for the Blue Jays. That outfield, along with solid starting pitching, led the Blue Jays to their first-ever American League East division title in 1985. Bell caught a fly ball, off the bat of Ron Hassey, for the final out in the 5–1 victory over the New York Yankees on October 5, clinching the division title for the Blue Jays. Despite Bell's .321 average in the ALCS, they lost the series to the Kansas City Royals.
His best season came in 1987 when the Blue Jays ultimately fell two games short of the Detroit Tigers in the division race. Bell finished with a .308 BA, .352 OBP, .608 SLG, 111 R, 47 HR and 134 RBI. He was awarded the American League MVP award that year.
On April 4, 1988, Bell became the first player in Major League history to hit three home runs on an opening day (all of them coming off of Bret Saberhagen), however, his play throughout the year declined as he conflicted with Blue Jays manager Jimy Williams, who wanted Bell to become the Jays' full-time designated hitter.
Bell had a bounce-back year in 1989, posting a .297 average, 18 HR and 104 RBI, helping the Blue Jays win their second division title. However, in the ALCS, he only hit .200 with one home run, as they lost the series to the Oakland Athletics. Bell became a free agent after the 1990 season and signed with the Chicago Cubs. After one year with the Cubs, he was traded across town to the Chicago White Sox for Sammy Sosa and Ken Patterson.
He played two years with the White Sox, recording 25 HR and 112 RBI in 1992. In 1993 his play declined, primarily due to a persistent knee injury. He was benched in the ALCS against his former team, the Blue Jays, and was released at the end of the season, after which he announced his retirement.
Bell was a powerful free-swinger, usually posting a good slugging percentage and relatively low strikeout rate, but a poor on-base percentage. He was known as a mediocre defensive player and played mainly as a designated hitter during the last two years of his career, despite his strong preference for playing in the field. Despite his success on the field, Bell had a love-hate relationship with the fans and media in Toronto, particularly in his later years as his declining defensive game came to overshadow his offensive talents. After the fans booed him for committing an error, he told the media that the fans could "kiss my purple butt." The next day a sign appeared in left field "George, we are behind you all the way." Bell's difficult relationship with the Toronto sports media was exacerbated by his reluctance to do interviews during his early years with the Blue Jays (which was due to his then-weak knowledge with the English language). Towards the end of his time in Toronto, however, Bell warmed to the media, who in turn began to soften their often harsh criticisms of his play and attitude.
On May 28, 1989, while with the Blue Jays, Bell hit a walk-off home run in a 7–5 victory over the Chicago White Sox in the final Major League game played at Exhibition Stadium. Bell also homered in the first game at the Blue Jays' new park, the SkyDome (now the Rogers Centre), on June 5, eight days later.
George Bell is currently enshrined in the upper deck of the Rogers Centre's Level of Excellence, devoted to players and personnel who have made a significant impact as members of the Toronto Blue Jays. He shares the honor with Tony Fernández, Joe Carter, Cito Gaston, Pat Gillick, Dave Stieb, Tom Cheek, Roberto Alomar, Carlos Delgado and Paul Beeston.
In 2004, he was inducted into the Caribbean Baseball Hall of Fame. In 2013, he was inducted into the Canadian Baseball Hall of Fame and Ontario Sports Hall of Fame.
Bell has eight children: four from his first marriage to Maria Peguero (Christopher, George Bell Jr, Kevin, and Randy) and four from his second marriage to Melida Bell (Dean, Shadeland, George Michael, and George Bryner). He is the older brother of former major leaguer Juan Bell.