After his freshman season at Tyler Junior College, where he had averaged 18.1 points, 7.7 rebounds, and 3.1 assists per game, Butler received interest from Division I programs.

[9] Butler accepted an athletic scholarship to attend Marquette, where, as a sophomore in the 2008–09 season, he averaged 5.6 points and 3.9 rebounds per game and recorded a free-throw percentage of 76.8%.

Butler had two game-winning shots versus UConn and St. John's, to help Marquette finish 11–7 in the Big East and earn its fifth consecutive NCAA tournament appearance.

[11] He set a franchise record when he played 60:20 in a triple-overtime game against the Orlando Magic on January 15 and finished with 21 points, seven rebounds and six assists.

[20] On April 20, Butler set a playoff career high for the second straight game, scoring 31 points in the Bulls' 91–82 win over the Milwaukee Bucks to take a 2–0 lead in their first-round series.

[21] On April 25, Butler again set a playoff career high with 33 points, in a Bulls' 92–90 loss to the Bucks, holding their series lead to 3–2.

[27] On January 3, Butler broke Michael Jordan's team record for points in a half, scoring 40 of his 42 after the break to lead the Bulls to a 115–113 win over the Toronto Raptors.

Butler had 10 rebounds and six assists while making 15-of-30 field goals and 21-of-25 free throws to help the Bulls end a three-game losing streak.

[32] He was voted to play in the 2016 NBA All-Star Game, but the injury forced him to drop out, and he was subsequently replaced by teammate Pau Gasol.

In 34 minutes of playing, he recorded 24 points, 11 rebounds, six assists and one steal in a 108–100 win, helping the Bulls break a four-game losing streak.

[34] He returned to the sidelines on March 7, for the team's game against the Milwaukee Bucks due to back soreness and swelling in his left knee.

[37] In the Bulls' season finale on April 13, Butler recorded his second career triple-double with 10 points, 12 rebounds and 10 assists in a 115–105 win over the Philadelphia 76ers.

[67][70] On November 12, 2018, Butler was traded, along with Justin Patton, to the Philadelphia 76ers in exchange for Jerryd Bayless, Robert Covington, Dario Šarić and a 2022 second-round draft pick.

[85] On August 31, in game 1 of the Eastern Conference semifinals, Butler scored a then playoff career-high 40 points on 13-of-20 shooting from the field in a 115–104 win over the first-seeded Milwaukee Bucks.

He became the sixth player with multiple triple-doubles in a finals series along with James, Magic Johnson, Larry Bird, Wilt Chamberlain and Draymond Green.

[91] Butler became only the second player in a finals series to lead his team in points, rebounds, assists, steals and blocks, joining James in 2016.

Together with teammate Bam Adebayo who posted 16 points, 12 rebounds and 10 assists, they became the first pair in league history to register triple-doubles in the same game more than once.

Butler became only the third player in franchise history to have at least 45 points, five assists and five rebounds in a postseason game, joining James and Dwyane Wade.

[107] On May 17, in game 1 of the Eastern Conference finals, Butler posted 41 points (27 in the second half), nine rebounds, five assists, four steals and three blocks in a 118–107 win over the Boston Celtics.

[118] On January 10, 2023, Butler tied his season-high with 35 points, along with seven rebounds, four assists, four steals and three blocks in an 112–111 win over the Oklahoma City Thunder.

The Heat set an NBA record by making all 40 of their free throws, the last of those coming on Butler's three-point play with 12.9 seconds left in the game.

[120] On March 11, Butler scored a season-high 38 points, including 15 in the final six minutes of the fourth quarter when Miami overcame a 15-point deficit.

[122] On April 14, Butler in his second play-in appearance scored a game-high 31 points to help the Heat take a 102–91 win over his former team, the Chicago Bulls, and secure the eighth seed for the playoffs.

[124] He moved to second place in 35+ point playoff games in Heat franchise history (10), surpassing LeBron James (9) and trailing only Dwyane Wade (14).

[127][128][129] In game 5 of the series against the Bucks, Butler recorded 42 points, eight rebounds, four assists and two steals in a 128–126 overtime win, leading the Heat to the second round of the playoffs.

[130][131][132] In game 1 of the Eastern Conference finals, Butler recorded 35 points, five rebounds, seven assists and a playoff career-high six steals in a 123–116 win over the Boston Celtics.

[134][135] In a narrow vote between him and Caleb Martin, Butler was named Eastern Conference Finals MVP, averaging 24.7 points, 7.6 rebounds, 6.1 assists and 2.6 steals per game.

He joined LeBron James and Dwyane Wade as the only players in Heat history to put up at least 500 points, 100 rebounds, and 100 assists in a single postseason run.

[140][141] On February 7, 2024, Butler recorded his 16th career triple-double with 17 points, 11 rebounds, 11 assists and three steals in a 116–104 win over the San Antonio Spurs.

[151] On February 6, 2025, Butler was traded to the Golden State Warriors in a five-team deal that sent a package headed by Andrew Wiggins to the Heat.