At the age of six, Kepler started baseball at the Little League level with the John F. Kennedy School in Berlin. Though he received a scholarship at age seven to the Steffi Graf Tennis Foundation, he decided he preferred baseball. Kepler attended John F. Kennedy School, and the St. Emmeram Academy in Regensburg in 2008, where he was able to train in baseball more than the average American teenager. He played association football with Hertha BSC, and played baseball for Buchbinder Legionäre Regensburg of Bundesliga, the highest baseball league in Germany.

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. At the age of 16, he signed with the Twins in 2009 for US$800,000, the largest signing bonus given by an MLB franchise to a European-born player. Kepler made his American debut in the Rookie-level in 2010 Gulf Coast League (GCL) with the GCL Twins. He was promoted to the Elizabethton Twins of the Rookie-Advanced Appalachian League in 2011. He was assigned to Elizabethton for the 2012 season. An elbow injury delayed the start of Kepler’s 2013 season, when he was assigned to the Cedar Rapids Kernels of the Class A Midwest League. Following the regular season, the Twins assigned Kepler to the Glendale Desert Dogs of the Arizona Fall League.

After the 2013 season, the Twins added Kepler to their 40-man roster and he was invited to spring training. Kepler played for the Fort Myers Miracle of the Class A-Advanced Florida State League in 2014, and opened the 2015 season with the Chattanooga Lookouts of the Class AA Southern League. Kepler was selected to represent the Twins at the 2015 All-Star Futures Game, though a sore shoulder prevented him from playing. Kepler finished the 2015 season with a .327 batting average, nine home runs and 18 stolen bases. He was named Southern League Player of the Year.

The Twins promoted Kepler to the major leagues on September 21, 2015 the night after the Lookouts won the Southern League championship. He made his major league debut on September 27, 2015 and recorded his first hit on October 4, 2015. After Donald Lutz, Kepler is the second German-developed player to play in the modern Major Leagues.

The Twins assigned Kepler to the Rochester Red Wings of the Class AAA International League to start the 2016 season. After playing in two games for Rochester, the Twins promoted him to the major leagues to replace the injured Danny Santana on April 10, 2016. Fifteen days later, Kepler was optioned to Rochester. On June 1, 2016 Kepler was recalled to replace the injured Miguel Sanó, and he began getting regular starts for the Twins in right field. The next day, Kepler had his first multi-hit game, and on June 12, Kepler swatted his first major league home run, a walk-off three-run shot in the 10th inning off of Matt Barnes of the Boston Red Sox. On August 1 against the Cleveland Indians, Kepler became the first European-born MLB player to hit three home runs in one game and the 5th Twins player to do so after Bob Allison, Harmon Killebrew, Tony Oliva and Justin Morneau. On August 8, 2016 Kepler was named co-American League Player of the Week, his first time receiving that honor, alongside teammate Joe Mauer.

Kepler started opening day against the Kansas City Royals, and collected a hit in his first at bat. In a game against the Chicago White Sox on August 31, Kepler came up to bat in the bottom of the ninth with the bases loaded. Opposing pitcher Juan Minaya threw a slider inside and Kepler got hit by the pitch and became the second player in Twins history to have a walk off hit by pitch. It gave the Twins their 20th win in August. Kepler finished the year with career highs in games played, with 147, batting average of .243, home runs with 19, and 69 RBI. In 2018, Kepler had a batting average of .224, hit 20 home runs, with 58 RBI, in 156 games. His 20 home runs and 156 games played were both career highs.

Kepler signed a 5 year, $35 million contract on February 14, 2019. He won his second American League Player of the Week award for the week of May 26th, he led the MLB that week in batting average, on base percentage and slugging percentage with a line of .571/.600/1.190. He had his second career three home run game against the Cleveland Indians on June 6, all three home runs came against starting pitcher Trevor Bauer. In a game against the Cleveland Indians on July 13, Kepler hit two home runs in his first two at bats against opposing starting pitcher Trevor Bauer, those two home runs were the fourth and fifth straight home runs hit against Trevor Bauer in consecutive at bats. This was the first time in MLB history that a batter hit a home run in 5 consecutive at bats against the same pitcher during a single season. On August 16, 2019 Kepler hit his 33rd home run of the season, setting a Major League record for home runs in a single season by a European born player, passing former Giants outfielder Bobby Thomson. He batted .252/.336/.519, and set career highs in home runs, runs and hits, he also led the major leagues in pull percentage (53.4%), and finished 20th in MVP voting.

Kepler started 2020 by hitting a home run on the first pitch of the season against the Chicago White Sox, following that with another home run in his second at bat. Max Kepler is the second player to hit a home run in the first two innings in a season following Ted Kluszewski of the Angels (April 11, 1961).