After signing with the Braves as an international free agent in 2014, Acuña made his MLB debut in 2018, and won the National League Rookie of the Year Award.

Since 2018, Acuña has made four MLB All-Star team appearances, won three Silver Slugger Awards, and twice led the league in stolen bases.

[17] Despite a .432 average and four home runs in spring training, Acuña was reassigned to minor league camp on March 19, 2018.

[20] This made him the youngest player in Major League Baseball at that time,[21] claiming the distinction from teammate Ozzie Albies.

[26] On May 28, Acuña was placed on the 10-day disabled list due to a mild ACL sprain and a bruise in his left knee as well as back contusion.

[30] While playing against the Miami Marlins on August 13, 2018, Acuña became the fourth player in the history of Major League Baseball to hit a home run to lead off both games of a doubleheader.

[35] In the finale of the Braves' series against the Marlins on August 15, Acuña faced José Ureña, who hit him with the first pitch of the game.

[40] Three days later, Acuña broke the team's leadoff home run record in a game against the Boston Red Sox.

[43] With his fifteenth stolen base on September 22, 2018, Acuña became the fourth player in MLB history to record a 25–15 season, while aged 20 or below, alongside Alex Rodriguez, Orlando Cepeda, and Mike Trout.

On October 7, in a National League Division Series game against the Los Angeles Dodgers, Acuña became the youngest player in MLB history to hit a postseason grand slam, aged 20 years 293 days, off Dodgers pitcher Walker Buehler.

[56] On August 9, Acuña hit his thirtieth home run of the 2019 season while facing Marlins pitcher Tayron Guerrero.

[71] On May 19, Acuña hit his first career walk-off home run against the New York Mets to give the Braves a 5–4 win.

[76] Acuña was elected to start the 2021 All-Star Game alongside teammates Freddie Freeman and Ozzie Albies[77] but was unable to participate due to the injury.

[81] Acuña remained at the Braves' spring training facility and played in simulated games until being assigned to the Gwinnett Stripers during the third week of April.

[89] In addition, Acuña was named the NL Player of the Month for June after slashing .356/.429/.683 with nine home runs and 14 stolen bases.

[90] On July 3, 2023, Acuña became the first player in MLB history to tally 40 stolen bases, 20 home runs, and 50 RBIs before the All-Star break.

[92] On August 31, Acuña joined the 30–30 club for the second time in his career (2019) by hitting a grand slam for his 30th home run of the season.

[93][94] On September 22, Acuña joined the 40–40 club for the first time in his career,[95] eventually becoming the first player in MLB history to record 40 home runs and 70 stolen bases in the same season.

[98] Acuña finished the regular season with a .337 batting average, 41 homers, 106 RBI, 73 steals, 217 hits, 149 runs and 383 total bases.

Shohei Ohtani won the American League equivalent, and, for the first time in the award's history, both AL and NL winners were selected unanimously.

[108] On May 26, Acuña suffered a leg injury while taking a lead from second base against the Pittsburgh Pirates and, after being tended to by team trainers, was able to walk off the field.

Initially believed to be knee soreness, the Braves later announced that an MRI showed a complete tear in his left anterior cruciate ligament and that he would miss the remainder of the 2024 season.

Former major league hitter Sean Casey compared Acuña's batting style to Roberto Clemente, as his natural core power and rotational torque allows him to hit without a backswing, keeping the knob of the bat pointing down at home plate (normally pointing towards the catcher during the backswing), yet still making contact and maintaining control of the barrel.

According to Harold Reynolds, who adopted the Rickey Henderson technique for both baserunning and fielding, the stance also stops him from leaning or tipping off-fielders for base stealing.