Gary Sheffield went 3-for-4 with an RBI and Miguel Cabrera had two triples for Detroit.
Relievers Bobby Seay, Zach Miner, Jason Grilli, Denny Bautista and Todd Jones each pitched scoreless innings for the Tigers.
"I like those zeroes on the bottom of the scoreboard," manager Jim Leyland said. "I know it's still spring training, but that pitching was the most satisfying thing to me."
It was the second shutout loss of the spring for Houston, which totaled only four hits.
Detroit scored in the first inning when Astros starting pitcher Wandy Rodriguez loaded the bases and gave up a run-scoring walk to Guillen.
Placido Polanco and Guillen hit two-run homers in the third.
Sheffield and Clete Thomas had RBI singles before Cabrera's two-run triple in the sixth inning made it 10-0.
Thomas, called up last week after outfielder Curtis Granderson broke a finger, has made the team, as has reliever Aquilino Lopez.
"Thomas has a lot of plusses. He has a great arm and is an outstanding runner. And some guys just look a little different in their uniforms. He looks like a big-leaguer," Leyland said.
Rodriguez went four innings and allowed five runs and seven hits with three walks. He struck out three.
"He couldn't command his fastball," Astros manager Cecil Cooper said. "Every time he pitched away, it would get away from him. I was a little concerned (about his health) because he couldn't get the ball down early.
"But he was healthy, that's the main thing. He got up to 78 or 80 pitches and that was good."
Woody Williams didn't fare any better, allowing five runs in only three innings. His spring ERA jumped to 11.32 but manager Cecil Cooper isn't giving up on the veteran.
"I thought he pitched OK," Cooper said of Williams. "One inning he got some balls up. The second inning they hit some balls pretty hard off of him. It wasn't as good as his last outing, but it was OK."
Williams wasn't pleased.
"The first and third innings were fine," he said. "It doesn't matter how hard you throw it or how soft you throw it, if you leave the ball up in the zone, these guys are pretty good hitters.
"I think I'm more than capable of going out there and pitching well. It's been one big inning every time I went out there this year except for one time."