Willson played as a tight end for Rice University each year from 2009 through 2012. His position coach at Rice was former Detroit Lions tight end David Sloan. After reporting late to camp in 2008 due to his baseball commitments in Canada, Willson redshirted as a true freshman.
Freshman season
Willson finished his redshirt freshman year with 7 receptions for 122 receiving yards and one receiving touchdown.
Sophomore season
He finished his sophomore season in 2010 with a total of 33 receptions, 425 receiving yards, and 3 receiving touchdowns.
Junior season
In 2011, he was selected to Phil Steele's midseason All-Conference USA team as tight end. He was selected to the Consensus first-team preseason All C-USA and also was selected to the first team of Dave Campbell's Texas Football All-Texas College preseason team before his junior season. He finished his junior season with 29 receptions, 313 receiving yards, and 3 receiving touchdowns.
Senior season
Willson finished his senior season in 2012 with a total of nine receptions for 126 receiving yards and two receiving touchdowns, which earned him a spot in the NFLPA Collegiate Bowl.
Professional career
Seattle Seahawks
Willson played in every game for Seattle in 2013 and scored his first touchdown against the San Francisco 49ers. At the end of the regular season, Willson was graded as the second most valuable rookie tight end by Football Outsiders, despite being the eighth tight end selected in the 2013 Draft. Willson's rookie season was capped with a blowout win in Super Bowl XLVIII. Willson caught two passes for 17 yards in the Seahawks' 43–8 victory over the Denver Broncos. Willson's second season in 2014 saw an increased role when starting tight end Zach Miller was injured after a Week 4 Super Bowl rematch against Denver, eventually ending up on injured reserve. Willson caught a game-winning 23 yard touchdown pass with less than a minute left in week 8 against the Carolina Panthers. He later starred in a week 16 game against the Arizona Cardinals, catching three passes for 139 yards and two touchdowns. Willson ended the season with 22 catches for 362 yards and three touchdowns. In that season's playoffs, Willson caught four passes for 68 yards and a touchdown in a divisional round game against the Carolina Panthers. A week later, he caught a key two-point conversion in the NFC Championship Game against the Green Bay Packers, as the Seahawks rallied to defeat the Packers 28–22 to reached consecutive Super Bowls. In Super Bowl XLIX, Willson had no catches as the Seahawks failed to repeat as champions, defeated by the New England Patriots, who rallied in the fourth quarter behind quarterback On March 17, 2017, Willson re-signed with the Seahawks.
Detroit Lions
After five years in Seattle, Willson signed a one-year, $2.5 million contract with the Detroit Lions on March 21, 2018.
Willson is a practicing Catholic who attributes his success in life to being a part of the Catholic Church. Willson had a Tuesday guest spot with BJ & Migs Mornings on 99.9 KISW "The Rock of Seattle" radio station titled "The End Zone with Luke Willson."