Jockey Mario Gutierrez, riding in his first Derby, guided the 3-year-old colt ahead of Bob Baffert's Bodemeister and a late closing Dullahan to win on a fast track.
It was trainer Doug O'Neill's first Derby victory. He had never finished better than 13th in the Derby with two other horses.
I'll Have Another, the Santa Anita Derby winner, went off at 15-1 in one the deepest and evenly balanced fields in recent years to win by 1½ lengths.
The chestnut colt, owned by J. Paul Reddam, finished the 11/4-mile race in 2:01.83 in front of a Derby-record crowd of 165,307.
The 20-horse field was expected to see a fast pace set by Trinniberg. Instead, Bodemeister rocketed right to the front through impossibly fast fractions. That pace proved his undoing.
Turning for home, Bodemeister, sent off at 6-1, held a clear lead — as much as five lengths — but the closers were starting to find their best ride as he began to weaken. The 9-2 race favorite, Union Rags, was squeezed between horses at the break, later ran into more traffic problems and was not a factor.
I'll Have Another paid $32.60, $13.80 and $9. Bodemeister returned $6.20 and $5.60 and Dullahan paid $7.20.