McDowell announced his decision to enter the draft with a message on social media Tuesday morning.
"This was a very difficult decision and I will always cherish my time in East Lansing," he said in a message posted to his Twitter account. "I want to thank my family, coaches, teachers, administrators and teammates. I'm ready to fulfill my childhood dream of playing in the NFL."
McDowell made 34 tackles and 1.5 sacks this season. He missed the last three games of the season with an ankle injury. The 6-foot-6, 275-pound defensive lineman is almost universally projected as a first-round pick in this spring's draft.
The Detroit-area native said this August that he didn't plan to enter the NFL unless he was projected as a top three overall pick. ESPN's Mel Kiper Jr. listed him as the No. 15 pick on his most recent "Big Board" last week.
McDowell's message said he promised his parents he would return to Michigan State to finish his degree in the future.
Spartans head coach Mark Dantonio said McDowell had a significant impact on the program's recent success, including a 2015 Big Ten title and trip to the College Football Playoff.
"Malik McDowell is an extremely gifted player who has demonstrated the ability and mindset to succeed at the next level," Dantonio said. "...We wish him the best and are excited for the opportunity in the next chapter of his life as he pursues his dream to play in the NFL."