On the same track where Breeders' Cup glory has eluded him, Game On Dude has claimed the Grade One Santa Anita Handicap for the third time.

Game On Dude snapped a three-race losing streak with his victory against seven rivals, including Mucho Macho Man and Will Take Charge who ran one-two in last year's Breeders' Cup Classic.

The Bob Baffert-trained Game On Dude beat Will Take Charge by 1-3/4 lengths to create history on his home track having won the race in 2011 and 2013.

"There's a lot of people who came to put their $2 on Game On Dude," Baffert said.

Game On Dude showed solid early speed, setting the pace along the rail. He responded to Mike Smith's urgings when challenged into the second turn.

"I was a little worried when those horses came to him," Baffert said. "Will Take Charge made a really bold move but the Dude wasn't going to give it up today."

Baffert was emotional watching the horse which has become like a member of his family.

"I was just in awe of the horse," he said. "When he gets in that groove no one can beat him. This horse has been so special. He's a pet around the barn."

Smith pumped his left arm as he arrived back in front of the stands to rousing cheers.

"When he shows up he can run with anybody in the world," Smith said. "We may throw in a dud every now and then, but he makes up for it."

The victory pushed Game On Dude's career earnings beyond $US6 million ($A6.62 million) and his record to 16 wins from 31 starts.