Geoff Blum doubled in three runs and the Astros handed the Diamondbacks only their third home loss in 13 games his season, 6-4 on Tuesday night.
The hard-throwing Scherzer, Arizona's 2006 first-round draft pick out of the University of Missouri, relieved Diamondbacks starter Edgar Gonzalez in the third.
Scherzer retired all 13 batters he faced, seven by strikeout, with a fastball that reached 98 mph on the Chase Field radar gun. It was the most strikeouts ever by an Arizona pitcher in his first big-league game.
"I was so anxious to get out there, so prepared to finally make my major league debut," he said. "I'm just happy to go out there and get it out of the way. I felt comfortable out there, not nervous at all. I just tried to go out there and do my thing."
Houston manager Cecil Cooper was impressed.
"You've got a guy throwing 98 and he had a nice slider to go with it," Cooper said. "He kept the ball down, and when he needed that extra he went and got it. That's a pretty good arm there. I'm just glad we got six and didn't need any more."
Arizona manager Bob Melvin brushed off questions about whether Scherzer would join the rotation.
"We'll take a look at it later," Melvin said.
Jose Valverde, who led the majors with 47 saves for Arizona last year and was traded to Houston in the offseason, pitched a scoreless ninth for his fourth save in seven opportunities. Valverde had pitches hit 97 and 98 mph, striking out Chris Burke and Eric Byrnes to end the game.
"Everybody knows this is my old team," he said. "I was excited. To strike out this guy and do it for the Houston Astros, it's emotional for me."
The Astros ended Gonzalez's night with a four-run third inning that put Houston up 6-2. Blum drove in three with a bases-clearing double, then scored on J.R. Towles' double to left that replays showed should have been ruled a home run.
"I know it's been few and far between when I've had the opportunities, but it's really nice to contribute, especially with the bases loaded and a team like that, to jump out to a relatively early lead," said Blum.
He also made a nice stop of Conor Jackson's hard grounder to start a double play in the sixth.
Gonzalez (1-2) allowed six runs on eight hits in 2 2/3 innings. Doug Brocail (1-0) threw 1 1/3 innings of scoreless relief to get the victory.
Jackson had three RBIs, including a two-run homer, for Arizona.
Houston starter Jack Cassel allowed three runs on four hits in 4 2/3 innings, falling one out shy of being eligible for the win. He was replaced after walking two batters.
"All I can say is I was confident I could get that last out," Cassel said.
The Astros jumped on Gonzalez for two runs in the first. Michael Bourn singled, then scored from first on Miguel Tejada's double. Tejada scored on Carlos Lee's two-out single off the glove of diving first baseman Jackson.
Cassel retired the first two batters in the Arizona first and had an 0-2 count on Orlando Hudson before the second baseman singled. Jackson followed with a shot into the left field seats, his sixth home run of the season, to tie it at 2-2.
Arizona got a run in the fourth when Hudson tripled and scored on Jackson's ground out, and another to cut it to 6-4 on pinch hitter Miguel Montero's RBI single in the seventh.
Cassel singled with two outs in the second and tried to score from first on Kazuo Matsui's double. But Stephen Drew's relay throw from Jeff Salazar easily got there ahead of the runner to end the inning.
Tejada and Lance Berkman singled with one out in the third, then Lee walked to load the bases for Blum, who was batting .206 entering the game with three RBIs.
Arizona RHP Micah Owings (4-0), who sprained his ankle Friday in San Diego, will return to the Arizona rotation with a start Friday night against the New York Mets. ... Scherzer struck out 38 and walked three, allowing three earned runs, in 23 innings with Triple-A Tucson. ... Cassel was making his sixth start and eighth appearance in the majors. His brother Matt is backup quarterback of the New England Patriots.