As a sophomore at the University of Georgia in 2009, Houston was a second team all-SEC selection after recording 7.5 sacks. As a Junior, Houston recorded 10 sacks, leading all linebackers in the SEC, and only second to Auburn's Nick Fairley who had 11.5 sacks as part of the defensive line, and was a first team all SEC selection and an All-American.
Houston was drafted 70th overall, in the third round, by the Kansas City Chiefs in the 2011 NFL Draft. Houston was originally projected to be a late first round pick, but it was reported that he tested positive for marijuana at the NFL Combine in February, which dropped him to the third round. After the season, Houston had 5.5 sacks and 49 tackles. His impressive play would lead him to win the Chiefs Mack Lee Hill Award. In week 6 of the 2012 NFL season, Houston had his first interception in his career.
Houston led the NFL in sacks in 2014 with 22, nearly breaking Michael Strahan's single season record of 22.5. This included a four-sack, five-tackle performance with a forced fumble in the season finale.
On March 3, 2015, the Chiefs placed a non-exclusive franchise tag, worth $13.195 million, on Houston, meaning that he can negotiate with other teams, but the Chiefs have the right to match any offer, or receive two first-round picks as compensation.
On July 15, 2015, hours before the deadline for long-term deals on franchise players, the Chiefs signed Houston to a six-year contract worth $101 million. The deal includes $52.5 million in guarantees.