The incident began when Greinke raced to cover first base on a ground ball off the bat of Astros second baseman Jose Altuve. The two reached the bag at exactly the same time. Holbrook gave the safe sign and Greinke slammed the ball into the ground in disgust.
Greinke said it was the first time a player had ever beaten him to first base.
"I threw a cutter away and thought [Altuve] hit a ground ball to second base, so I didn't think about covering first at the beginning. And then realized what was going on, ran over real quick. He beat me to the bag.
"I got real mad at myself because it's a mental mistake. I think it's the first time I've not covered first on a ball hit to that side. So I was just really mad with myself.
"I don't know why I threw the ball down. I never make mental mistakes like that."
Holbrook almost immediately gave Greinke the hook. The two exchanged words before Roenicke raced from the dugout to voice his displeasure. Holbrook didn't take long to toss the Brewers' manager.
It was the fourth time in his career that Greinke has been ejected -- twice before for throwing at batters and once for yelling at an umpire from the dugout. He said he doesn't blame Holbrook for giving him the boot after spiking the ball.
"I didn't mean it toward him," Greinke said. "But I shouldn't have done that. I didn't think about it at the time that there was anything wrong with it. But then after looking back at it, that definitely didn't look good. It definitely didn't look how I meant it. So I put the umpire in a bad position and he had to make a decision."
Roenicke, however, was not so forgiving.
"I don't have any problem with him kicking me out," he said. "He should have kicked me out. But I do have a problem with [him kicking out] Zack."
Roenicke said he felt Holbrook wasn't in a proper position to make such a game-changing call.
"He said he thought Zack showed him up," Roenicke said. "I saw the replay. I talked to Zack. Zack was mad at himself for not covering first base. [Holbrook] overreacted. He didn't even see what happened.
"Zack was behind him. He didn't even see [Greinke] spike the ball. And you need to know. You need to know 100 percent what happened if you're going to kick out a starting pitcher after four pitches in a ballgame."
The Brewers never recovered.
"It's definitely a blow," Roenicke said. "You've got your guy out there pitching. Zack's been pitching great for us. And we're taken out of a game in the first inning and trying to scramble and figure out what we're going to do."
The Astros built a 6-0 lead against seven Milwaukee pitchers. A three-run third inning did most of the damage. Houston third baseman Scott Moore ignited the explosion with a leadoff homer in the third.
"It was obviously huge, but then I feel like that just swung momentum in our direction," said Astros left fielder J.D. Martinez, who equaled a career high with three hits.
Houston leadoff hitter Jordan Schafer, who had two hits and scored twice, agreed.
"He's a Cy Young winner and to be able get him out of there and face their bullpen, that really helps you," Schafer said.
If there is a silver lining, it would be in the prospect of bringing back Greinke to start Sunday's series finale. Roenicke said he's spoken with both Greinke and with scheduled starter Marco Estrada about that possibility.
"We've talked about it and we'll talk some more," Roenicke said. "We're not positive which way we're going to go. We'll know tonight which way we'll go."
"It would be a shame to completely waste a day I should be pitching," Greinke said.
The Brewers came into Saturday's game second in the National League with 100 homers. Only Colorado (102) has more. But the Crew was limited to just seven singles in six innings, two from Aramis Ramirez. Included in that was an eighth-inning bunt single by Corey Hart before Cody Ransom followed with a pinch-hit RBI double. It was Milwaukee's only extra-base hit of the game.
Norichika Aoki extended his hitting streak to 14 games with an infield single in the third inning, legging out a dribbler down the first-base line.