He played college basketball for the Louisville Cardinals where he received the Karl Malone Award in 2015 as a junior for being the top power forward in the nation.

[2] As a freshman, Harrell backed up power forward Chane Behanan, averaging 5.7 points and 3.6 rebounds in 16.2 minutes per game.

In his reserve role, Harrell helped the Cardinals win the 2013 NCAA championship, which was later vacated,[3] to cap his freshman season.

[1] With Gorgui Dieng's departure for the 2013 NBA draft, Harrell received recognition in the offseason leading to his sophomore year as one of the top returning players in the country.

[4] He and teammate Russ Smith received postseason honors, being named to the American Athletic Conference's all-conference first team.

[6] Harrell decided to stay for his junior season instead of opting for the NBA, and the Cardinals moved to the Atlantic Coast Conference (ACC).

[7] In the 2014–15 season, he averaged 15.7 points and 9.2 rebounds per game and was the inaugural winner of the Karl Malone Award, given to the nation's top power forward.

[11] He made his debut for the Rockets in the team's season opener against the Denver Nuggets on October 28, recording eight points and three rebounds in a 105–85 loss.

[15] During his rookie season, he received multiple assignments to the Rio Grande Valley Vipers, the Rockets' G-League affiliate.

[20] On June 28, 2017, the Los Angeles Clippers acquired Harrell, Patrick Beverley, Sam Dekker, Darrun Hilliard, DeAndre Liggins, Lou Williams, Kyle Wiltjer, and a 2018 first-round pick from the Houston Rockets in exchange for Chris Paul.

[40] On February 10, 2022, Harrell was traded to his hometown team the Charlotte Hornets in exchange for Ish Smith, Vernon Carey Jr., and a 2023 second-round pick.

[46] However, on August 2, he suffered an anterior cruciate ligament (ACL) injury while preparing for the training camp[47] and was waived on October 23.

[49] On September 12, 2024, Harrell signed with the Adelaide 36ers of the National Basketball League (NBL) in Australia as an injury replacement player for Jarell Martin.

[56] In 2012, Harrell was a member of the United States team at the FIBA Americas Under-18 Championship that won Gold in São Sebastião do Paraíso, Brazil.

[60] Harrell left the 2020 NBA Bubble in Walt Disney World for a family matter, which was later revealed to be to tend to his grandmother, who died soon after.