Miguel was signed by the Marlins in 1999 as an amateur free agent and came up through their farm system, teaming with future major leaguers Adrián González and Dontrelle Willis.

He began his professional career in 2000 as a shortstop in the Gulf Coast League (GCL). After batting .260 with 10 doubles, two triples, and two home runs through 57 games for the GCL Marlins, Cabrera was promoted to Class-A ball where he finished the final eight games batting .250 with 6 RBIs for the New York–Penn League (NYPL) Blue Sox in Utica, New York. While playing that winter for the Tigres de Aragua in the Venezuelan Winter League, manager Bill Plummer moved Cabrera from shortstop to third base.

Cabrera finished the 2008 season with a career-high 37 home runs, which led the American League. He became the youngest AL home run champion since Troy Glaus in 2000. He also established a new career high in RBIs (127). He became one of only six players who had driven in at least 100 runs in each of the past five seasons, joining Alex Rodriguez, Albert Pujols, David Ortiz, Bobby Abreu, and Mark Teixeira.

Heading into 2001, the Marlins bumped Cabrera up to the Low Class-A Kane County Cougars. He earned his way into the Futures Game during All-Star Weekend in Seattle, along with González. He ended the year batting .268 with 30 extra-base hits, 66 RBIs, and distinguished himself as having the strongest arm in the Midwest League.

Cabrera made his major league debut on June 20, 2003, at 20 years old; Édgar Rentería, at 19 years old, was the only Marlins player to make his debut at a younger age. Cabrera hit a walk-off home run in his first major league game against the Tampa Bay Devil Rays, following Billy Parker in 1972 and Josh Bard in 2002 as the third player since 1900 to hit a game-winning home run in his big-league debut. Cabrera rapidly established himself, as his stellar play in July made him the Marlins’ cleanup hitter. Cabrera’s postseason play helped propel Florida to the World Series title over the New York Yankees and landed him on the cover of ESPN The Magazine during the offseason. He finished fifth in the NL Rookie of the Year voting, as teammate Willis took home the award.

In Game 4 of the 2012 World Series, Cabrera hit his first World Series home run since his rookie year with the Marlins in 2003, putting Detroit on the board for the first time in two games. During the bottom of the 10th inning, Cabrera was the final out of the World Series as he struck out looking, completing the San Francisco Giants’ sweep of the Tigers.

In 2004, Cabrera batted .294 with 33 home runs, 112 RBIs, 101 runs, 177 hits, a .366 on-base percentage, a .512 slugging percentage from the third and fourth spots in the order, while playing in 160 games and earning his first All-Star appearance.

In 2005, Cabrera finished second in the National League in base hits with 198, and batted .323 with 33 home runs, 43 doubles, two triples, and 116 RBIs. He was voted to his second consecutive All-Star Game, along with teammates Paul Lo Duca and Willis, and won his first Silver Slugger Award. cabrera’s 33 home runs made him the youngest player in Major League Baseball history with back-to-back 30 homer seasons, at 22 years, 143 days. Albert Pujols performed the feat at 22 years, 223 days. Cabrera also became the first Marlin in history to hit at least 30 home runs and drive in at least 100 runs in back-to-back seasons.

On June 22, 2006, pitcher Todd Williams let the first pitch of an attempted intentional walk get too close to the plate and Cabrera reached out and singled it to right center field. The hit occurred during the 10th inning, scoring the winning run to give the Marlins a 6–5 lead over the Baltimore Orioles.

Cabrera is both a Catholic and a practitioner of Santería. He became a babalawo in the 2006 offseason. His wife is named Rosangel, and they have two daughters and one son, born August 2011. Cabrera’s wife filed for divorce in April 2017, but later changed her mind. Cabrera also has two other children, who he fathered with an ex-mistress, a boy and a girl (who in January 2019 were six and three years old), who lived in Orlando, Florida.

On September 15, 2007, in a game against the Colorado Rockies at Coors Field, Cabrera drove in at least 100 runs for the fourth consecutive year. His 100th RBI came in the first inning against Ubaldo Jiménez. Five innings later, Cabrera added four more RBIs when he hit a ball 438 feet (134 m) into the center field trees for his first career grand slam. He joined David Ortiz, Alex Rodriguez, Albert Pujols, Mark Teixeira, Bobby Abreu, and Vladimir Guerrero as the only players to reach the 100-RBI plateau in each of the four previous seasons.

In 2007, Cabrera won the NL Player of the Week twice (April 1–8 and June 4–10). He also passed former Marlins Gary Sheffield and Derrek Lee for second on the franchise home run list. Cabrera moved into third in all-time franchise RBIs and first in batting average. Cabrera ended the season with career highs in both home runs and runs batted in.

On December 5, 2007, the Marlins traded Cabrera and starting pitcher Dontrelle Willis to the Detroit Tigers for pitchers Andrew Miller, Dallas Trahern, Eulogio De La Cruz and Burke Badenhop, outfielder Cameron Maybin, and catcher Mike Rabelo.

On March 22, 2008, Cabrera reached an agreement with the Tigers on an eight-year, $152.3 million contract extension. At the time, the deal was the fourth-largest in baseball history, behind those signed by Alex Rodriguez, Derek Jeter, and Manny Ramirez. The deal was also the largest in Tigers history at the time, surpassing the five-year, $75 million contract signed by Magglio Ordóñez in 2005 (it was later surpassed in 2012 when Prince Fielder signed a nine-year, $214 million deal) Cabrera earned $11.3 million in 2008, and was to receive an average of $20 million per year through 2015.

Cabrera made his Tigers debut on March 31, 2008, playing third base in a home game against the Kansas City Royals. In his third at-bat, he hit a solo home run off Royals pitcher Gil Meche. He finished the game 1-for-5 with two strikeouts, and the Tigers lost 5–4 in 11 innings.

Cabrera continued a torrid pace into the 2013 season, being named American League Player of the Month for May. Cabrera batted .379 (44-for-116) with nine doubles, 12 home runs, 33 RBIs, 23 runs scored and 15 walks in 28 games to claim his third career Player of the Month Award. Cabrera previously won top player honors in July 2008 and August 2012. The week of August 5–11, Cabrera was named the American League Co-Player of the Week, with fellow Tigers teammate Austin Jackson. Cabrera batted .429 (12-for-28) with two doubles, four home runs, 11 RBIs and seven runs scored over seven games, to win his 10th career player of the week award.

On August 23, 2009, Cabrera hit his 200th career home run in his 1,000th career game against the Oakland A’s. He became only the fourth Venezuelan player to ever reach that plateau.

On January 21, 2010, it was reported that Cabrera spent three months in an alcohol abuse treatment center to help him recover from his addiction. He said at the time he had not consumed any alcohol since he was taken into custody in October 2009, and that he would continue his treatment into spring training and the regular season.

Cabrera was named to his second AL All-Star team as a reserve in 2011, his sixth All-Star Game appearance overall. On July 15, the first game after the All-Star break, Cabrera collected his 1500th career hit, in a game against the Chicago White Sox. Cabrera hit for a .344 average, winning the AL batting title, while also leading the AL in on-base percentage (.448) and doubles (48). He had his eighth straight 100-RBI season (105) and fifth straight 30-HR season (30). He also reached a career-high in walks with 108. On defense, Cabrera led all AL first basemen in errors, with 13.

Cabrera hit .429 with six home runs and 21 RBIs in September 2011, propelling the Tigers into the playoffs and eventually the American League Championship Series. In the 2011 ALCS, Cabrera hit .400 with four doubles, three home runs and seven RBI, and posted a 1.606 OPS, but the Tigers fell to the Texas Rangers in six games.

Through 2011, he had the sixth-best career batting average of all active players (.317), and seventh-best slugging percentage (.555) and OPS (.950).

Cabrera was arrested in Florida on suspicion for drunken driving and resisting arrest on February 16, 2011.

In 2012, after the signing of first baseman Prince Fielder, the Tigers announced Cabrera would move back to third base. In a pre-season game against the Philadelphia Phillies, Cabrera was struck below the right eye by a ground ball off the bat of Hunter Pence, which broke a bone. Despite this, after seeing the team’s orbital surgeon, Dr. Srinivas Iyengar, Cabrera believed he would be ready for opening day on April 5. He was, and was in the starting lineup on Opening Day.

Cabrera is very active in the community, and in 2012 he began The Miguel Cabrera Foundation to help a variety of children’s funds. He also uses his foundation to encourage young kids to play baseball and softball. In 2012 and 2013, Cabrera was nominated by his team for the Roberto Clemente Award, honoring the MLB player who best represents baseball on and off the field.

Baseball Hall of Famer Al Kaline was quoted in 2013 as saying that Cabrera’s performance was “unbelievable”, and that Cabrera was already qualified for Cooperstown himself.” Bob Nightengale of USA Today Sports called Cabrera “the greatest player in the game of baseball.” Barry Bonds agreed with Nightengale’s analysis, adding “He’s the best. By far. Without a doubt. The absolute best.”

Cabrera won the ESPY Award in 2013 for Best MLB Player. On July 9, 2013, he hit his 350th career home run, against the Chicago White Sox.

On March 28, 2014, the Tigers announced that Cabrera had signed an eight-year contract extension worth $248 million. Combined with the $44 million the Tigers owed on the remaining two years of Miguel’s then-current contract, the total 10-year commitment was worth $292 million. The deal broke the previous record commitment of $275 million the New York Yankees tendered to Alex Rodriguez in 2007. Cabrera’s contract has since been surpassed by Giancarlo Stanton’s 13-year, $325 million contract in 2014, the largest contract in baseball. Many analysts criticized the contract as excessive and short-sighted, with The Washington Post calling it “the worst.”

Cabrera won the ESPY Award for Best MLB Player for a second year in a row in 2014.

Cabrera finished the regular season with a .313 batting average, 25 home runs, 109 RBI and a league-leading 52 doubles; he led both leagues with 11 sacrifice flies. Along with Matt Holliday in 2014, Cabrera attained at least 20 HR, 30 doubles, 75 RBI, and 80 runs scored each for the ninth consecutive season, becoming the fourth player in MLB history to do so. The others were Stan Musial, Manny Ramirez, and Pujols, all with ten consecutive seasons.

On May 16, 2015, Cabrera hit his 400th career home run, against Tyler Lyons of the St. Louis Cardinals, making him the all-time leader in home runs among Venezuelan-born players, surpassing the previous record holder, Andrés Galarraga. At the age of 32 years, 28 days, he became the third-youngest active player to reach this milestone, behind Albert Pujols (30 years, 222 days) and Alex Rodriguez (29 years, 316 days), and the eighth-youngest in history.

Although Cabrera had only 18 home runs and 76 RBI in 2015, snapping his streak of 11 consecutive seasons with at least 25 home runs and 100 RBIs, his .338 batting average led the major leagues and earned him his fourth AL batting title in the last five years. He was the seventh player in history to win four AL batting titles, following Ty Cobb, Harry Heilmann, Wade Boggs, Rod Carew, Ted Williams, and Nap Lajoie. He also led the American League with a .440 on-base percentage, and ranked second in the league with a .974 OPS. He led all MLB hitters (140 or more plate appearances) in batting average against right-handers, at .344.

On May 4, 2018, Cabrera was placed on the 10-day disabled list due to a right hamstring strain. On June 12, Cabrera suffered a left biceps injury after swinging and immediately left the game. He suffered a rupture in his left biceps tendon, requiring surgery and putting him out of action for the remainder of the 2018 season. He finished the 2018 season with a .299 batting average, three home runs, and 22 RBIs in 38 games.

In 2018, Cabrera was in a Florida court litigating a case brought against him in August 2017 by his former mistress, Belkis Mariella Rodriguez, over a dispute regarding how much child support Cabrera should pay Rodriguez for two children they had together. She argued that given his $30 million annual salary, she was entitled to $100,000 a month. Cabrera had been paying Rodriguez $20,000 a month in child support without any court order, but cut the amount by $5,000 in the summer of 2017. In December 2018 the Orange County Circuit Court ordered Cabrera to pay $20,000 a month in child support to the ex-mistress, additional expenses, and her attorneys fees.

Cabrera struggled with knee issues in 2019, which had the Tigers moving him into a full-time designated hitter role by early June. He hit .282 for the year with 12 home runs and 59 RBI in 139 games. His .398 slugging percentage was the lowest of his career.

On August 29, 2020, Cabrera collected three hits in a doubleheader against the Minnesota Twins passing former Tiger Charlie Gehringer for 50th on the all-time MLB hits list with 2,841. This made Cabrera one of only 16 major league players to place in the top 50 all-time for hits, home runs and RBIs. On August 30 against the Twins, Cabrera recorded his 2,000th career hit as a Tiger, becoming the eighth Tiger player to reach the milestone.

For the 2020 season, Cabrera hit .250 (the second-lowest batting average of his career)/.329/.417 with a team-leading 10 home runs and 35 RBIs in 57 games. Through season’s end, he ranked 23rd all-time in doubles (581), 23rd in total bases (4,942), 24th in RBIs (1,729), 30th in home runs (487), and tied for 46th in hits (2,866). He had the slowest sprint speed of all major league DHs, at 23.2 feet per second.