Zambrano (1-0) pitched one-hit ball into the eighth inning and had two singles and an RBI to help the Chicago Cubs deal Milwaukee its first loss of the season, 4-0 on Saturday.
Zambrano gave up only a two-out line single in the second inning to Russell Branyan and shut down a Brewers lineup that scored 25 runs in the first three games. He struck out six and walked two while outpitching fellow Opening Day starter Ben Sheets (1-1).
But after throwing just one pitch to the second hitter of the game, Junior Spivey, Zambrano stepped off the mound, pointed to his pitching arm and signaled for Cubs trainer Mark O'Neal.
Zambrano was allowed three additional warm-up tosses. He then struck out Spivey on the next three pitches and cruised until being relieved by Chad Fox with one out in the eighth.
"It happens to me all the time," Zambrano said, referring to the cramp. "I have to drink more water. It has nothing to do with my elbow or shoulder."
Cubs manager Dusty Baker, whose team snapped a three-game losing streak, said the same thing happened to Zambrano in a game last season.
"I'm just glad it was muscle and nothing else," Baker said. "He was throwing great from the beginning. He hit well, he ran well, he did everything well today.
"He wanted the victory and knew we needed it. His fastball was moving," he said.
Jeromy Burnitz hit a solo homer in the sixth and Todd Walker added a two-run double in the seventh for the Cubs. That gave
Zambrano, who had singled in the game's first run in the second, some room to work.
After giving up Branyan's single, Zambrano retired 10 straight before walking J.J. Hardy to start the sixth. Through the first seven innings, he retired the Brewers in order five times.
"I hit a fastball down in the zone," Branyan said. "He threw the heck out of the ball. We had some good contact, but he was tough."
The Brewers were the last remaining undefeated team in the major leagues.
"(Zambrano) was throwing that heavy slider 96-97 miles an hour with an occasional breaking ball and even a couple of good changeups," Brewers manager Ned Yost said. "He was dead on. (Today) shows you why he's one of the best pitchers in the National League."
Zambrano started the Cubs' opener at Arizona last Monday. He allowed three runs on seven hits in 4 2/3 innings and did not get a decision in Chicago's 16-6 win.
"(Monday) I tried to be too perfect," Zambrano said. "Today I had good command of all my pitches and got ahead in the count. That was the difference."
Sheets (1-1) allowed four runs and eight hits in seven innings.
Zambrano's two-out RBI single in the second scored Burnitz and gave the Cubs a 1-0 lead.
Burnitz lofted his first homer with the Cubs into the right-center field bleachers with one out in the sixth to make it 2-0.
Walker doubled off the base of the right-center field wall with one out in the seventh to drive in Zambrano and Corey Patterson.
Zambrano threw 111 pitches, 64 for strikes ... The Cubs will decide on Sunday whether right-hander Mark Prior starts at home against San Diego or in the minors on Tuesday. ... In his Opening Day start at Pittsburgh last Monday, Sheets allowed two runs and seven hits in seven innings.