[10] On June 2, 2010, against the Cleveland Indians, Jackson made a difficult over-the-shoulder running catch in the ninth inning of Armando Galarraga's near-perfect game.

The perfect game eventually ended with two outs in the ninth after an incorrect call by umpire Jim Joyce.

[13] On November 15, 2010, Jackson came in second in the 2010 American League Rookie of the Year voting, behind Rangers closer Neftalí Feliz.

[14][15] Jackson finished his rookie season by playing 151 games with a .293 batting average, 10 triples, 4 home runs, 41 RBI, and an AL-leading 170 strikeouts.

On April 5, 2012, Jackson was the leadoff hitter and played center field on Opening Day for the Tigers, where he went 3–5 with an RBI and a run.

Jackson hit a walk-off, bases-loaded single down the third base line to give the Tigers the win over the Red Sox, 3–2.

Jackson went to the postseason with the Tigers for a second straight season, and he hit a home run in the series-clinching Game 4 against the New York Yankees in the ALCS.

On January 17, 2014, Jackson and the Tigers avoided arbitration by agreeing to a one-year deal for the 2014 season worth $6 million.

[21] On August 31, 2015, the Mariners traded Jackson to the Chicago Cubs for a player to be named later and an international signing bonus slot.

[23] On August 25, White Sox GM Rick Hahn told the media that Jackson would miss the rest of the season after he had been out since June 10.

On August 1, 2017, Jackson robbed Hanley Ramirez of a home run by making a spectacular catch over the right center field wall.

On January 22, 2018, Jackson signed a two-year deal with the San Francisco Giants worth $6 million over two years.

[31] On September 29, he hit a walk-off double in the 13th inning on David Wright's final career game, giving the Mets a 1–0 victory.