On January 15, 2009, Harvin announced he would forgo his remaining college eligibility and participate in the 2009 NFL Draft. Harvin finished his college career as one of the most prolific offensive threats in school history. In three seasons, he totaled 133 catches for 1,929 yards and 13 touchdowns, while rushing the ball 194 times for 1,852 yards with 19 touchdowns. His 32 career touchdowns is the most ever by a University of Florida wide receiver. He averaged an astounding 9.5 yards per carry as a running back and averaged 11.6 yards overall (running back, receiver, return man). He was the first player in University of Florida history to rush for 100 yards and have 100 yards receiving in the same game (against Vanderbilt, 2007).
In February 2009, Harvin tested positive for marijuana at the NFL Combine. Some teams reportedly removed him from their potential draft rosters.
On April 25, 2009, Harvin was selected by the Minnesota Vikings with the 22nd overall pick in the first round of the 2009 NFL Draft, the fourth wide receiver selected in the draft. Following extended contract negotiations, on August 3, 2009, Harvin signed a five-year contract worth up to $14.5 million, including $8.7 million in guarantees. Harvin wore jersey #12 for the Minnesota Vikings.
Harvin caught his first touchdown pass September 13, 2009 in the season opener against the Cleveland Browns, thrown by quarterback Brett Favre. He ended his first career NFL game with a total of 36 yards receiving and 22 yards rushing. On September 27, Harvin had a 101-yard kickoff return for a touchdown against the San Francisco 49ers. With this touchdown, Harvin became the first Viking ever to score a touchdown in each of his first three games as well as the second youngest player to return a kickoff for a touchdown in NFL history (21 years, 122 days). On October 25, 2009, Harvin had an 88-yard kickoff return for a touchdown against the Pittsburgh Steelers. He finished the regular season with 60 receptions and eight touchdowns, two on kickoff returns, and a rushing average of nine yards per carry.
After a stellar first year in the NFL, Harvin suffered a string of illnesses. On April 30, 2009, while en route to a Minnesota Vikings rookie mini-camp, Harvin fell ill and was hospitalized prior to changing planes in Atlanta. He was released from the hospital the following day. Vikings coach Brad Childress said Harvin was dehydrated and had a virus. Additionally, Harvin did not participate in the 2009 NFL Rookie Symposium due to illness and also missed the team's first three practices and first two days of training camp at Minnesota State University, Mankato. Further, Harvin did not play in the Vikings 30-10 victory over the Cincinnati Bengals in week 14 due to migraine headaches, which also prevented him from practicing the following week. However, he did play in the Vikings week 16 overtime loss to the Chicago Bears, but missed two postseason practices before the New Orleans Saints playoff game, due to migraine headaches. On August 19, 2010, he passed out during practice due to a migraine attack and was taken to a local hospital in an ambulance. He was discharged from the hospital the following day but remained on the sidelines in practice.