Trailing 3-2, Carlos Delgado singled to open the eighth off Mike Mohler (3-3) before Cruz hit his fifth homer over the left-field fence.
"I like hitting fifth," said Cruz. "I hit fifth towards the end of last year and I did OK, and it's good to know that no matter what happens your going to be there no matter what, and that eases a lot of things," Cruz said.
Cruz is batting .357 (10-for-28) with seven extra-base hits and eight RBIs since being recalled from Triple-A Syracuse on July 30.
"I've been feeling good and hopefully I can keep it going as long as possible," he said.
Before being sent down to the minors, the 24 year-old outfielder was hitting .214 while batting mostly in the seventh and eighth spots.
"You can see it in his face that he's confident," Toronto manager Tim Johnson said. "I'm very proud of him and hopefully we got the player we all thought we knew he could be."
Paul Quantrill (2-4) got the win with 1 1-3 innings of relief.
Mohler spoiled a strong outing by A's starter Mike Oquist, who was pounded by the New York Yankees for 14 runs and 16 hits in just five innings in his last start.
Oquist allowed just one earned run and six hits in 5 2-3 innings.
"I had to bounce back and I did," Oquist said. "Mentally, it's tough to come back from something like that, but I gave my guys a chance today."
Toronto starter Roger Clemens lasted seven innings, allowing two earned runs and five hits. He walked three and struck out eight.
Clemens didn't allow a hit until A.J. Hinch doubled with one out in the fifth. One out later, Bip Roberts hit an RBI single to break a 1-1 tie.
Ben Grieve reached on an infield single, and Matt Stairs followed with an RBI single to give the A's a 3-1 lead.
Two errors by Toronto second baseman Craig Grebeck allowed the A's to score in the third. But Oakland gave it right back in the bottom of the inning on an error by former Blue Jay third baseman Ed Sprague.
Craig Grebeck cut the A's lead to 3-2 with an RBI single in the sixth.
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