The horse beat out 20 competitors in the event dubbed "The Greatest Two Minutes in Sports," at the famed Churchill Downs in Louisville on Saturday.
Lead by jockey Mario Gutierrez, the undefeated Nyquist took the top prize, beating out frontrunners Exaggerator and Outwork. He's the eighth Derby undefeated Derby winner since 1915 – the most recent being 2008's Big Brown.
Two-time Derby-winner and Dancing with the Stars vet Victor Espinoza failed to take home a victory with Whitmore, who had 20-1 odds going into Saturday's race. Espinoza would have been the first jockey to win three consecutive Derbys. He won the Triple Crown last year on American Pharaoh, and the 2014 Kentucky Derby on California Chrome.
Trojan Nation, the only horse in the Derby who has never won a race, remained defeated.
A crowd sporting in Derby hats and sipping mint juleps cheered on as Nyquist was gifted the famous garland of roses, which weighs over 40 pounds and includes over 400 hand-sewn roses.
The winner's trophy, called "priceless" by Churchill Downs, is made of 14-karat solid gold.
Nyquist now has a chance to compete for the Triple Crown if it can secure wins at the Preakness on May 21 and the Belmont Stakes on June 11.