It was the first career multi-homer game for Donaldson, who reached base five times on the night.
"He was the catalyst for a great offensive night," said manager Bob Melvin. "Every at-bat was terrific."
"Those two, he didn't miss," added starter Scott Kazmir. "Those things were tape-measure shots, so it was fun to watch."
But one really stood out.
Donaldson's second homer, coming in the seventh inning with his club already leading by seven, wasn't so much necessary as it was gratifying for the A's side.
Six days after A's shortstop Jed Lowrie was nearly hit twice by a pitch from right-hander Paul Clemens, the Astros reliever plunked Lowrie in the backside. During a game last week, Houston manager Bo Porter took offense to Lowrie's decision to bunt in the first inning with a 7-0 lead.
Clemens was immediately ejected, and Donaldson responded by homering on the third pitch he saw from Anthony Bass.
"I love it," said Lowrie, smiling wide. "I love it."
Antics aside, the A's simply kept hitting their way to a win in this one, moving back into a first-place tie with the Rangers in the American League West. They're 24-5 all-time against the Astros and have outscored them, 29-8, in four wins in as many tries this year.
The victory, awarded to Kazmir after another impressive outing, also ensured the A's of their 11th consecutive winning month dating back to June 2012. At 14-8, they've matched their best start in franchise history after 22 games, first achieved in 1992.
Kazmir, pitching in front of about 40 friends and family members in his hometown, labored out of the gate and walked in a run in the first inning. By the end of two, he had already thrown 47 pitches, but he proceeded to face just one over the minimum in his final four innings, scattering five hits with two walks and seven strikeouts in the six-inning outing.
Oakland's $22 million southpaw is 3-0 with a 1.62 ERA, the sixth lowest mark in the AL. He has 31 strikeouts in 33 1/3 innings.
"It's important to be able to have that foundation early in the year and be able to kind of build on it throughout every start," Kazmir said. "I'm kind of in and out on how I feel stuff-wise, but just to stay within myself and make the adjustments as the game goes on is big for me."
His teammates, meanwhile, sent at least five men to the plate in each of the first seven innings, with Donaldson getting things going in the opening frame with his first homer. He has six on the season.
Alberto Callaspo also homered in the game, collecting a two-run shot in the third inning, following an RBI hit from Derek Norris.
Lowrie was 3-for-4 with two doubles and an RBI, and Craig Gentry reached base four times, forcing the Astros to commit four of their five errors in his at-bats.
Each of the A's starting nine was on base at least once, though Yoenis Cespedes' time on the bags was brief, as Oakland's left fielder exited in the seventh inning with a strained left hamstring after legging out an infield single. He's expected to be out of action for a few days.
On this night, at least, Donaldson provided enough power for the both of them.
"It was neat," Oakland's third baseman said. "I told [Ryan Cook] yesterday I was going to hit three today. I fell one short. That was just kind of in fun, but it was nice to have a good day today, especially after the last three days."