He played in Major League Baseball (MLB) for the Boston Red Sox, Florida / Miami Marlins, Los Angeles Dodgers, and Cleveland Indians.

[18] After the 2005 season, the Red Sox traded Ramírez, along with Aníbal Sánchez, Jesús Delgado, and Harvey García, to the Florida Marlins in exchange for Josh Beckett, Mike Lowell, and Guillermo Mota.

On April 3, he recorded his first Major League hit in his first at-bat of the season, a single to center field off of Houston Astros pitcher Roy Oswalt.

[citation needed] Ramírez's 46 doubles in the 2006 season is the all-time NL record for a shortstop aged 22 or younger.

He became just the fifth big-league player since 1900 to hit at least 45 doubles and steal at least 50 bases, joining Ty Cobb, Tris Speaker, Craig Biggio, and Lou Brock.

[24] In a game against the Cincinnati Reds on July 22, 2007, Ramírez overextended his shoulder when he tried to hit a pitch on the low outside corner off right-hander Bronson Arroyo.

[26] Entering the 2008 season, after the Marlins traded All-Stars Miguel Cabrera and Dontrelle Willis to the Detroit Tigers, Ramírez was now one of the faces of the franchise.

[28] Ramírez hit his 30th home run of the season on September 13 and joined Preston Wilson as the only Marlins to become members of the 30–30 club.

On September 6, against the Nationals, Ramírez hit his 100th home run of his MLB career, becoming the fourth quickest shortstop in terms of games played to reach that milestone (Alex Rodriguez, Nomar Garciaparra, and Ernie Banks).

On September 15 in a game against the Philadelphia Phillies, Ramírez aggravated an injury in his elbow he had sustained earlier in the season while swinging.

He injured himself after trying to make a diving catch in a game against the New York Mets on August 2, aggravating a shoulder injury that had plagued him in 2010.

During the 2011–2012 off-season, the Marlins, during their rebuilding stage, acquired shortstop José Reyes, who was the reigning National League batting champ.

On July 25, 2012, Ramírez was traded to the Los Angeles Dodgers with Randy Choate in exchange for Nathan Eovaldi and minor league pitching prospect Scott McGough.

[38] His return from the disabled list reignited the Dodgers offense and they started to get hot, which included a 46–10 record from mid-June to mid-August and they went from last place to winning the National League West.

[39] In the 2013 National League Division Series against the Atlanta Braves, Ramírez went 8 for 16 with six extra-base hits, tying a franchise postseason record.

He ended Clayton Kershaw's bid for a perfect game on June 18 by committing a throwing error in the top of the seventh inning.

After the error, manager Don Mattingly replaced Ramírez with SS Carlos Triunfel for defensive purposes.

[42] On Opening Day of the 2015 season, in his first game with Boston in almost 10 years, Ramírez played left field for the first time in his career and hit two home runs (one of them a broken-bat grand slam[29]) for a total of 5 RBI as the Red Sox routed the Philadelphia Phillies 8–0.

[45] Ramírez ended the 2015 season with a .249 batting average and 19 home runs in 401 at-bats,[46] while his defense in left field was rated as the worst in the American League.

Ramírez reported early to 2016 spring training with the Red Sox and dismissed his impending positional switch to first base as nothing hard.

Once the season began, the transition was well received by the press and clubhouse, with praise going to his improved defense and greater comfort in the infield.

[48] On July 20, 2016, Ramírez belted three two-run home runs in Boston's 11–7 interleague play victory against the San Francisco Giants at Fenway Park.

[49] Then on August 12, he hit a pair of three-run home runs as the Red Sox beat the visiting Arizona Diamondbacks, 9–4, in an interleague game.

[50] On September 15, 2016, in perhaps the most memorable at-bat of his season, Ramírez hit a walk off three-run home run to stun the Yankees and complete a thrilling comeback victory.

Ramírez, Mookie Betts and David Ortiz became the first trio in Red Sox history with 30 home runs and more than 100 RBIs in the same season.

[54] With the retirement of David Ortiz and the offseason addition of first baseman Mitch Moreland, Ramírez took on the role of designated hitter for the Red Sox.

[55] In the postseason, Ramírez batted 8-for-14 (.571) in the 2017 ALDS as the Red Sox lost to the eventual World Series champions, the Houston Astros.

On May 25, Ramírez was designated for assignment by the Red Sox as the team activated Dustin Pedroia from the disabled list.

[65] In June 2018, shortly after his release by the Red Sox, Ramírez was briefly reported to have a possible connection with a federal and state investigation into a drug ring based out of Lawrence, Massachusetts.

[58] Within days, it was clarified that Ramírez was not linked to the investigation and that a person arrested in the case had used his name "to get the cops off his back, which didn't work.