Big Brown, to be ridden by Kent Desormeaux, will start from the outside post position when the field of 20 horses compete in the nation's top thoroughbred racing attraction.
A chance of isolated thunderstorms are forecast for the 1 1/4-mile race at Churchill Downs.
Big Brown has been raced three times and won all three by a total of 29 lengths. He was the wire-to-wire winner in the Florida Derby.
Trainer Steve Asmussen will send out two horses -- Pyro and Arkansas Derby runner-up Z Fortune.
Pyro had been an early favorite for the Kentucky Derby after capturing the Louisiana Derby. Then came a last-place finish at the Blue Grass Stakes. Pyro received odds of 6-1 and will break from the No. 9 position.