[5] Kepler attended John F. Kennedy School,[3] and the St. Emmeram Academy in Regensburg in 2008, where he was able to train in baseball more than the average American teenager.

[3][8] Andy Johnson, an international scout working for the Minnesota Twins of Major League Baseball (MLB), first noticed Kepler when he played in a junior national tournament at the age of 14.

[9] An elbow injury delayed the start of Kepler's 2013 season, when he was assigned to the Cedar Rapids Kernels of the Single–A Midwest League.

[10] Following the regular season, the Twins assigned Kepler to the Glendale Desert Dogs of the Arizona Fall League.

[11] After the 2013 season, the Twins added Kepler to their 40-man roster to protect him from the Rule 5 draft, and he was invited to spring training.

[13] Kepler was selected to represent the Twins at the 2015 All-Star Futures Game,[14] though a sore shoulder prevented him from playing.

[21] After playing in two games for Rochester, the Twins promoted him to the major leagues to replace the injured Danny Santana on April 10.

[23] On June 1, Kepler was recalled to replace the injured Miguel Sanó, and he began getting regular starts for the Twins in right field.

This also made him the fifth Twins player to hit three home runs in a game, along with Bob Allison, Harmon Killebrew, Tony Oliva, and Justin Morneau.

[26] Kepler was named co-American League Player of the Week on August 8, sharing the honors with Twins teammate Joe Mauer.

Kepler was an Opening Day starter for the first time in 2017, collecting a hit in his first at-bat of the season against the Kansas City Royals.

[29] He went 1-for-3 with a double and a walk in the 2017 American League Wild Card Game, but the Twins were defeated by the New York Yankees.

[30] Kepler hit a walk-off home run against Brad Peacock of the defending champion Houston Astros on April 11, 2018.

[35] This was the first time in Major League history that a batter homered in five consecutive at bats against the same pitcher during a single season.

[20] Kepler was the Twins lead-off hitter on opening day, homering against Chicago White Sox starter Lucas Giolito on the first pitch of the season.

[38] This made him the second player in Major League history to hit a home run in the first two innings of a season, following Ted Kluszewski of the Angels (April 11, 1961).