He played college basketball for Baylor University and represented the United States at the 2013 Summer Universiade in Kazan, Russia.

As a sophomore in 2006–07, he averaged 13.5 points, 10.5 rebounds and 5.1 blocks per game, earning All-District 16-4A first team honors.

As a senior in 2008–09, he averaged 19.5 points and 6.2 rebounds per game, leading Killeen to three straight 30-win seasons and four consecutive district championship.

[2] On June 26, 2014, Jefferson was selected with the final pick in the 2014 NBA draft by the San Antonio Spurs.

[10] On March 6, Jefferson recorded his first career double-double with season-highs of 12 points and 13 rebounds in over 15 minutes of action in a 108–100 overtime loss to the Phoenix Suns.

[15] After impressing head coach Jeff Hornacek and general manager Ryan McDonough during preseason, Jefferson made the Suns' opening night roster for the 2015–16 season.

[16][17] He made his debut for the Suns on November 14, recording 2 points and 2 rebounds in a 105–81 win over the Denver Nuggets.

[22] The next day, he made his debut for the Jam in a 132–111 win over the Oklahoma City Blue, recording 18 points, 14 rebounds, 3 assists and 1 block in 34 minutes.

[38] Jefferson made his debut for the Long-Lions on the same day, scoring 17 points with six rebounds and a block in a 133–92 win over the Beikong Fly Dragons.

[39] On February 11, 2019, Jefferson parted-way with the Long-Lions after his import player roster spot was replaced by Lorenzo Brown.

[40] On February 22, 2019, Herbalife Gran Canaria of the Liga ACB announced the signing of Jefferson.

[42] On February 22, 2020, Jefferson signed with Atléticos de San Germán of the Puerto Rican league.