"Anytime you [allow] a six-run inning, it's difficult to come back from," manager A.J. Hinch said. "But what do we do? We come back and get four and make it a game."
Mike Fiers labored into the sixth inning, allowing four runs, and the Astros' bullpen gave up another four in the frame, putting Houston down 8-2.
But the team with 35 come-from-behind wins in 2015 nearly added another behind the three late-inning home runs.
"It's great to see," Fiers said. "This team never thinks we're out of a game."
Following Oakland's six-run outburst, Villar unloaded on a 1-0 fastball from A's starter Felix Doubront in the seventh, sending it into the second deck down the left-field line.