While attending the University of Illinois at Urbana–Champaign, Spence played for the Illinois Fighting Illini football team from 2009 to 2012. After redshirting in 2009, he started all 13 games at defensive tackle alongside All-AmericanCorey Liuget. He had 45 tackles, four tackles for a loss, one quarterback sacks, two hurries and one fumble recovery on the season. In 2011, he started all 13 games on the season, he finished ranked fourth on the team with 69 tackles on the season, including 5.5 tackles for a loess and 1.5 sacks. As a redshirt junior, he started all 12 games in 2012 and started all 38 games of his college career at defensive tackle. He ranked third on the team in tackles with 72 and tied for second on team with 7.0 tackles for a loss and had one sack. Spence announced on December 19, 2012 that he would forgo his senior season and enter the NFL Draft.
Professional career
Tampa Bay Buccaneers
On April 27, 2013, Spence was drafted by the Tampa Bay Buccaneers in the fourth round of the 2013 NFL Draft. The Buccaneers signed him to a rookie contract on May 15, 2013. Spence signed his contract on May 15, 2013, a four-year deal that’s worth $2,644,424. Spence collected a $484,424 signing bonus. On December 26, 2015, the Tampa Bay Buccaneers placed Spence on injured reserve.
On March 10, 2017, Spence signed a three-year, $9 million contract with the Detroit Lions. He started 11 games during the 2017 season, recording 39 tackles, three sacks and a forced fumble. Spence was named the 2017 recipient of the Detroit Lions Media-Friendly Good Guy Award by the Detroit chapter of the PFWA and Detroit Sports Media.
On May 3, 2018, Spence was traded to the Miami Dolphins for a conditional 2019 seventh round pick, previously acquired from the Browns in a trade for Jarvis Landry. On August 27, 2019, Spence was released from the Miami Dolphins.
On October 25, 2019, Spence was signed by the Jacksonville Jaguars.
Personal life
On January 14, 2014, Spence was arrested in Flomaton, Alabama on charges of misdemeanor marijuana possession. He was later suspended one game by the NFL for the incident. During the 2017 NFL season, Spence participated in a protest during the national anthem. Following this, he reported that his father, a contractor, was denied work due to his protest.