He played in Major League Baseball (MLB) for the New York Yankees, Atlanta Braves, San Francisco Giants, Toronto Blue Jays, Chicago White Sox, Kansas City Royals, Cleveland Indians, and Pittsburgh Pirates.

[2] He was promoted to the Tampa Yankees of the Class A-Advanced Florida State League, where he hit .288 with 51 RBIs in 85 games to finish the season.

At the end of June, he was promoted to the Columbus Clippers of the Triple-A International League, where he hit .324 with three homers and 11 RBIs in nine games.

[6] The next day he went 2-for-3 against Cleveland Indians pitcher Cliff Lee, scoring his first major league run, but then went 0-for-his-next-13 and made costly miscues,[7] including one on July 15, 2005, against the Boston Red Sox at Fenway Park, misplaying a Trot Nixon fly ball that resulted in an inside-the-park home run during a 17–1 defeat.

[9] Cabrera saw a lot of time in spring training of 2006 with starting outfielders Johnny Damon and Bernie Williams playing in the World Baseball Classic.

[10] He started the season strongly at Triple-A Columbus, hitting .385 with four home runs and 24 RBIs in just 31 games before being called up on May 9, 2006, after left fielder Hideki Matsui broke his wrist and was on the disabled list until September 12, 2006.

[12] On June 6, 2006, in the eighth inning of a 2–1 game against the Red Sox, he made an outstanding catch in left-center, leaping over the wall to take a home run away from Boston slugger Manny Ramírez.

MLB claimed to have seen video showing Cabrera punching superstar Tampa third baseman Evan Longoria during the brawl, and suspended him for two games along with teammate Shelley Duncan.

In early August, Yankee manager Joe Girardi demoted him to fourth outfielder, making Damon the everyday center fielder again.

[34] On December 9, 2010, Cabrera signed a one-year, $1.25 million contract with the Kansas City Royals,[35] eager for an opportunity to start consistently and hit in the middle of the lineup.

[36] On November 7, 2011, the Royals traded Cabrera to the San Francisco Giants for Jonathan Sánchez and minor league pitcher Ryan Verdugo,[37] seeking to bolster their starting rotation and free up center field for Lorenzo Cain.

[44] On August 15, 2012, Cabrera was suspended for 50 games without pay for testing positive for high levels of testosterone, suggesting usage of MLB-proscribed performance-enhancing drugs.

[a][50] As the Giants clinched a postseason berth, Cabrera's suspension officially expired during the 2012 National League Championship Series.

[53][54] In a game against the Detroit Tigers on April 9, 2013, Cabrera recorded his 1,000th career hit, a single off starter Aníbal Sánchez.

[55] Cabrera battled a sore hamstring and quadriceps muscle through the first two months of the regular season, but the injuries did not warrant time on the disabled list.

In early June, it was reported that Major League Baseball would be pursuing suspensions for players implicated in the Biogenesis scandal, including Cabrera.

[61] Cabrera returned from the disabled list on July 21 and played in 10 games before going back on the 15-day DL with irritation in his left knee.

[66] On September 7, Toronto general manager Alex Anthopoulos told reporters that Cabrera had undergone a successful surgery to remove a benign tumor from his lower spine on August 30, and that a full recovery was expected.

[69] He hit his only home run in the final game of spring training, a two-run shot to help the Blue Jays win 2–0 over the New York Mets on March 29 in Montreal.

[70] On April 4, 2014, Cabrera became the first MLB player to bat against Masahiro Tanaka, and hit a lead-off solo home run off of him.

[72] Cabrera broke a Blue Jays team record on April 13, by hitting in his 13th consecutive game to open the season.

[75] Cabrera recorded his 500th career RBI on July 26, 2014, to aid the Blue Jays in breaking their 17-game losing streak at Yankee Stadium.

On August 10, Cabrera drew a team-record five walks in a 6–5 win over the Detroit Tigers in 19 innings; the longest game in franchise history.

He also became the first player to reach base eight times in one game (the aforementioned five walks along with three hits) since Hall-of-Famer Rod Carew did so in 1972.

[77] He remained in the game but came out during his next at-bat in the sixth inning and was taken for x-rays, where it was determined that he had broken his right little finger and would require surgery,[77] ending his 2014 season.

Coming to the end of his two-year contract with the Blue Jays, Cabrera expressed a desire to re-sign with Toronto.

[78][82][83] In his first season with the White Sox in 2015, Cabrera played 158 games batting .273 with 36 doubles, 12 home runs, and 77 RBIs.

[85] In his third year with the White Sox before being traded to the Kansas City Royals, Cabrera batted .295 with 13 home runs and 56 RBIs in 98 games.

On February 10, 2019, Cabrera signed a minor league contract with the Pittsburgh Pirates that included an invitation to spring training.