Mine That Bird was kept along the rail around the turn for home and went past his last rival at the top of the stretch. He won by 6 3/4 lengths over Santa Anita Derby champ Pioneer of the Nile.
Illinois Derby winner Musket Man was third and Arkansas Derby champion Papa Clem fourth. The 7-2 favorite Friesan Fire finished next to last.
Mine That Bird covered the 1 1/4 miles on a sloppy track in 2:02.66.
Mine That Bird was a 50-1 long shot in the 19-horse field. The 3-1 I Want Revenge was scratched Saturday morning with an injured left front ankle.
It was the second Kentucky Derby victory for Borel, who also won in 2007 with Street Sense. Borel won Friday's Kentucky Oaks with Rachel Alexandra by more than 20 lengths.