The 2014 Kentucky Derby and Preakness Stakes winner was produced on the outside to score a four-length victory to win the richest prize in thoroughbred racing -- $6 million.
The massive payout makes five-year-old California Chrome America's all-time highest-earning racehorse with $12.4 million, surpassing the mark of Curlin, winner of the Dubai World Cup in 2008.
The convincing victory also makes up for the disappointment of being beaten into second place in the 2015 edition by Irish-bred Prince Bishop, and matches the prediction of 78-year-old trainer Art Sherman, who said his horse would be five lengths better this year .
The race was the finale to a lucrative nine-race card at Meydan Racecourse, with $30m at stake in total.
California Chrome, so close to the famed 'Triple Crown' in 2014, had been preparing under Sherman in Dubai for over five weeks even taking part and winning a handicap race last month.
He was a fitting winner of a race which came of age with its 21st staging, a massive crowd enjoying the top quality racing and the thriving social scene at Meydan.
16-1 shot Mubtaahij ran fine race to come second with Hoppertunity at 25-1 in third.
Frosted, runner-up at the 2015 Belmont Stakes as the great American Pharoah, ridden by Espinoza, completed the Triple Crown last year, disappointed after being sent off joint 15-8 favorite with California Chrome.
The prestigious penultimate race, the Dubai Sheema Classic, went to favorite Postponed (4/5), from second favorite Duramente by two lengths.
After taking the lead at the final corner, last year's King George winner never looked like being caught and racked up a fourth victory in a row.