As a follow-up to his victory in the Kentucky Derby, trainer Art Sherman's horse justified his stature as the overwhelming favorite by outrunning Ride On Curlin to the finish Saturday.
He covered the 1 3-16th mile course in 1:54.84.
Ride On Curlin finished second and Social Inclusion took third.
It was the first Preakness victory for the 77-year-old trainer. California Chrome has won six straight races.
The chestnut colt is the first California-bred horse to win the Preakness since Snow Chief in 1986.
With a victory in the Belmont on June 7, California Chrome will become the 12th Triple Crown winner in horse racing history and the first since Affirmed in 1978.