A native of Pittsburgh, Pennsylvania, Donald attended Penn Hills High School. He was selected first team All-State Class AAAA in each of his final two seasons, and compiled 63 tackles, 15 tackles for loss and 11 sacks as a senior. He also started at offensive guard.
As a freshman, Donald played in all 13 games as a reserve defensive tackle. He recorded 11 tackles, including three for loss, and two sacks. In 2011, as a sophomore, Donald moved into the starting lineup, and turned in a breakout campaign. He recorded 47 tackles, including 16 for loss, 11 sacks and one forced fumble, and was named a second-team All-Big East selection. As a junior, he recorded 64 tackles, including 18.5 for loss, 5.5 sacks, and one forced fumble, earning first-team All-BIG EAST honors. In his senior season, he became one of the most productive defensive players in the entire NCAA. He posted 59 tackles, including a career best 28.5 for loss, 11 sacks and four forced fumbles. He was named the ACC Defensive Player of the Year and was a unanimous All-American.
At the NFL Combine he set the record for fastest time for a defensive tackle previously held by Tank Johnson, who ran a 4.69 in 2004. Donald drew comparisons to John Randle afterwards. He was selected by the St. Louis Rams in the first round of the 2014 NFL Draft with the 13th pick overall.
After recording 47 tackles, nine sacks and two forced fumbles, he was one of three rookies selected to the 2015 Pro Bowl. On January 31, 2015, it was announced that Donald had won the 2014 NFL Defensive Rookie of the Year award.