Wiltjer was ranked as the No. 18 recruit in the class of 2011 in the ESPNU 100, the No. 25 recruit by Rivals.com, and the No. 22 recruit by Scout.com. He chose to play basketball for the University of Kentucky Wildcats and coach John Calipari on August 28, 2010. He had also considered Kansas, California, Texas, Gonzaga, Georgia Tech, and Wake Forest. Although he was a 5-star recruit according to all of the recruiting analysts, Kyle Wiltjer never started a game his freshman season at Kentucky, and did not play as many minutes as fellow freshmen Anthony Davis, Michael Kidd-Gilchrist, and Marquis Teague. He averaged only 11.3 MPG and 4.8 PPG, although his 3-point percentage was an impressive 42.5%. The Kentucky Wildcats won the 2012 NCAA championship during Wiltjer's freshman year. Wiltjer began the 2012–13 season as a starter. In his third game of the season, against Lafayette, he accumulated 23 points, 2 assists, and 4 rebounds. However, he would eventually settle into an off-the-bench role, being named the SEC's Sixth Man of the Year. In April 2013, he had announced he would remain at Kentucky for his junior season. However, he eventually changed his mind, posting a letter on Kentucky's official athletic website on June 23 indicating that he would transfer in order to "compete the way I know I can.... wherever that may be." A later report indicated that Wiltjer had drawn interest from three of the four Division I programs in his home state of Oregon, Gonzaga, Stanford, and Texas. According to that report, "he left the door open to return to Kentucky if he can't find the right situation." On July 19, multiple media outlets reported that Wiltjer had chosen Gonzaga. The transfer became official the next day, when Gonzaga received a signed copy of a financial aid agreement. After sitting out the 2013–14 season due to NCAA transfer rules, he had two remaining seasons of eligibility. In February 2015 he scored a career-high 45 points against Pacific. Wiltjer led Gonzaga to its second ever Elite Eight appearance and a school record 35-3 record. He was named a Consensus Second-Team All-American, as well as First-Team All-WCC and WCC Newcomer of the Year. In his first season with Gonzaga he appeared in 38 games averaging 16.8 points per game, 6.2 rebounds per game and 1.9 assists per game in 27.6 minutes per game. After contemplating forgoing his remaining eligibility to enter the 2015 NBA draft, WIltjer decided to return to Gonzaga for his senior year. Entering his second season with Gonzaga, Wiltjer was named CBS Sports' preseason player of the year. Sports Illustrated projected Wiltjer as the preseason player of the year, scoring champion, and the top-usage player in all of NCAA Division 1 basketball. He was named to the 35-man midseason watchlist for the Naismith Trophy on February 11.
Wiltjer's father, Greg, is a former Canadian professional basketball player. His paternal half-sister and Greg's daughter, Jordan Adams, is also a former professional player. Both Greg and Adams also represented Canada.
