He played college basketball for one season with the LSU Tigers, after which he was named a consensus first-team All-American and the USBWA National Freshman of the Year.

As the result of a holdout from the 76ers following the 2020–21 season, which led him to be traded to the Brooklyn Nets, Simmons is the most-fined player in NBA history, in terms of total financial loss.

Simmons left school to enter the NBA draft, becoming the third Melbourne-born number one overall pick in 11 years, alongside Andrew Bogut and Kyrie Irving.

In April 2013, he helped Montverde rally from a 16-point deficit to beat New Jersey's St Benedict's 67–65 in the final of the High School National Tournament.

[10] After competing in the Jordan Brand Classic International Game,[22] he returned to Melbourne, where he joined the Bulleen Boomers of the Big V competition in June 2013.

Montverde finished the season with a 28–0 record, closing with a 71–62 victory over Oak Hill Academy in the High School National Tournament at Madison Square Garden.

[29][30] On 10 March 2015, he was named the Morgan Wootten Award winner, given annually to the best male McDonald's All-American player who exemplifies outstanding character, exhibits leadership, and embodies the values of being a student-athlete in the classroom and in the community.

[37][38][39] Entering his freshman year of college, Simmons began his career on a four-stop national tour in Australia with the LSU Tigers.

[44] On 13 November 2015, Simmons made his college debut in LSU's season opener, recording a double-double with 11 points and 13 rebounds as a starter in a win over McNeese State.

[45] On 2 December, he helped LSU break a three-game losing streak by recording 43 points, 14 rebounds, 7 assists, 5 steals, and 3 blocks in a 119–108 win over North Florida.

[46] After recording 14 points and 10 rebounds in a win over Kentucky on 5 January 2016, Simmons was dubbed the best all-round player since LeBron James by NBA Hall of Famer Magic Johnson.

[48] Following the conclusion of the regular season, Simmons was named first-team All-Southeastern Conference and the league's Freshman of the Year on the 2016 Coaches SEC voting.

[62][63] While he shot the ball poorly during his first three Summer League games, Simmons was praised for his court awareness and passing ability for a big man.

[79] On 15 March against the New York Knicks, Simmons recorded his second consecutive triple-double and joined Robertson and Magic Johnson as the third rookie in NBA history to reach 1,000 points, 500 rebounds, and 500 assists.

[112] In game two of the 76ers' first-round playoff series against the Brooklyn Nets, Simmons had his second career postseason triple-double with 18 points, 12 assists, and 10 rebounds to lead Philadelphia to a 145–123 win.

[114] On 23 October 2019, in the 2019–20 NBA season opener against divisional rivals the Boston Celtics, Simmons scored 24 points on 68 percent shooting and recorded nine assists and eight rebounds in a 107–93 win.

[116] On 7 December, Simmons scored a career-high 34 points, while making 12 out of 14 shots, in a 141–94 win over the Cleveland Cavaliers, which included his second NBA career three-pointer.

[131][132] Following a Game 7 loss in the Eastern Conference semifinals against the Atlanta Hawks, Simmons came under heavy scrutiny due to his inability to shoot and lack of aggressiveness on offense.

[142] Simmons had previously been fined $1.4 million due to his absence from four preseason games, missed practices, on-court workouts, and meetings.

[144][145] Due to the repeated fines for missed games, Simmons became the most-fined player in NBA history,[146] with reports suggesting he had surpassed $10 million by the end of 2021.

[147] In January 2022, the 76ers reportedly had limited their fining of Simmons in response to him attending team meetings and counseling sessions,[148] but continued to dock him for missed games.

[149] Simmons subsequently filed a grievance to recoup nearly $20 million in salary withheld from him by the 76ers, and the two sides settled in August 2022 for an undisclosed amount.

[150] On 10 February 2022, Simmons was traded, along with Andre Drummond, Seth Curry, and two future first-round picks, to the Brooklyn Nets in exchange for James Harden and Paul Millsap.

[152] On 4 April, Nets head coach Steve Nash ruled out Simmons for the remainder of the regular season and the play-in tournament.

[173] On February 13, Simmons made his Clippers debut, putting up 12 points, seven rebounds, six assists, three steals, and one block in a 120–116 overtime win over the Utah Jazz.

[176] In July 2014, Simmons was added to the Boomers extended squad for the 2014 FIBA Basketball World Cup,[177] but did not make the final 12-man roster.

[178] Since 2013, Simmons has verbally stated that he would play for Australia on multiple occasions (including the FIBA World Cup and the Olympics), but has always withdrawn from the team before competition.

[180] On 15 May 2019, Simmons confirmed he would represent Australia in the 2019 FIBA World Cup and multiple exhibition games against Canada and the United States.

[194][195][196] His sister Emily, a former member of the Washington State University women's rowing team,[6] who has worked for Klutch Sports since 2014,[57] is married to former NFL player Michael Bush.

[198] In November 2016, Simmons was featured in the Showtime documentary film One & Done, providing an insight into his time as a one-and-done college player, as well as exploring his and his family's thoughts on the NCAA and the NBA's "one and done" rule.