He played college basketball for the Florida Gators, where he was a freshman member of their NCAA national championship team in 2007.

[3] Speights began his career at the University of Florida in 2006–07, and averaged approximately four points and two rebounds in six minutes per game as a freshman for the national champion Gators.

[6] In his rookie season, Speights had a field-goal percentage of .502 from the field, playing 79 games, shooting .773 from the free throw line, and notching two starts.

Speights' second season with the 76ers started off on a high note, as he saw a slight increase in playing time and put up good numbers.

In the fourth quarter of the November 14 game versus the Chicago Bulls, Speights injured his left knee.

Known for his defensive-minded coaching philosophy, this shift in team focus adversely affected Speights, who was known more for his offensive capabilities.

On January 4, 2012, Speights was acquired by the Memphis Grizzlies as a part of a three-team trade that sent Xavier Henry to the New Orleans Hornets and two future second round picks to the Philadelphia 76ers.

[9] On January 22, 2013, Speights was traded to the Cleveland Cavaliers, along with Wayne Ellington, Josh Selby, and a future first round draft pick, in exchange for Jon Leuer.

In the second round, Speights helped the Warriors defeat the Portland Trail Blazers in five games to qualify for the Western Conference Finals.

In their conference finals match-up with the Oklahoma City Thunder, the Warriors fought back from a 3–1 deficit in the series to win clinch a 4–3 victory.

[19] On October 30, 2017, he scored 18 points and hit a career-high six 3-pointers, including five in a six-minute span, in a 115–99 win over the New Orleans Pelicans.