Harris attended Half Hollow Hills High School West and joined the varsity basketball team as an eighth grader.

He played at Half Hollow Hills West until 2008 when he transferred to Long Island Lutheran Middle and High School in Brookville, New York for his junior year.

He then transferred back to Half Hollow Hills West for his senior year and went on to earn the 2010 Mr. New York Basketball award.

[5] On February 21, 2013, Harris was traded, along with Doron Lamb and Beno Udrih, to the Orlando Magic in exchange for JJ Redick, Gustavo Ayón and Ish Smith.

[8] On February 7, 2014, Harris scored a game-winning dunk at the buzzer against Oklahoma City in what has been called one of the most exciting finishes in Orlando Magic history.

[16][17] The Pistons finished the regular season as the eighth seed in the Eastern Conference with a 44–38 record, earning a playoff berth for the first time since 2009.

On December 23, 2016, Harris came off the bench for the first time in 2016–17 and subsequently scored a season-high 26 points in a 119–113 loss to the Golden State Warriors.

[22] On January 29, 2018, Harris, along with Avery Bradley, Boban Marjanović, a future protected first-round draft pick and a future second-round draft pick, was traded to the Los Angeles Clippers in exchange for Blake Griffin, Willie Reed and Brice Johnson.

On January 27, 2021, Harris hit a game-winning pull-up jump shot with 3.7 seconds left to help the 76ers hold off a comeback by the Los Angeles Lakers in a 107–106 victory.

[37] On April 16, 2022, during Game 1 of the first round of the playoffs, Harris logged 26 points and six assists in a 131–111 win over the Toronto Raptors.

[45][46] Harris is close friends with former NBA center Boban Marjanović, who was his teammate in Detroit, Los Angeles and Philadelphia from 2016 to 2019.

[47] Harris wears number 12 as a tribute to his close friend and former teammate Morgan Childs, who died at age 17 from leukemia.

He created the "Tobias Harris School of Mentoring Program" and partnered with the Yes We Can Community Center and UAS Inc to help athletes and their parents with the recruiting and scholarship process.

[51] Harris launched the Tobias Lit Labs campaign which brings books and authors to families and schools.

He has donated $10,000 to the Kappa Alpha Psi Foundation to provide grants for scholarships, community projects and after-school programs.