Marmol, making the appearance originally scheduled for Kerry Wood, pitched six strong innings in his first major league start and Perez, playing in place of injured third baseman Aramis Ramirez, hit his first homer of the season and drove in three runs to lead Chicago to a 9-3 win over the Cincinnati Reds.
"The first pitch, I was nervous," Marmol said. "After that, it was like pitching in Double-A. It was exciting."
Phil Nevin and Ronny Cedeno also homered and Cedeno had a career-high three RBIs for the Cubs, winners of three straight for the first time since April 23-25.
Marmol (1-0), who got the start when Wood was placed on the 15-day disabled list on Friday, gave up just one run and two hits. He walked three and struck out seven in his third career appearance.
"He was throwing strikes," Reds second baseman Brandon Phillips said. "He did a nice job. He had a little slider-curve. Whatever it was, you couldn't see the spin on the ball."
The Reds got runners on base in every inning except the first against Marmol, but he held them hitless in five at-bats with runners in scoring position.
"He was aggressive with his fastball, and he was able to use his breaking ball," Chicago pitching coach Larry Rothschild said. "When he makes mistakes, he knows what to do and can adjust. He's a great athlete."
Perez was making his fourth start of the season at third base as Ramirez got the day off after being hit in the left elbow by a pitch Saturday night. He responded by doubling his career homers and RBI against Reds starter Eric Milton, against whom he was hitting .148 (4-for-27) with one home run and three RBI coming into the game.
"I'm not anywhere close to Aramis," Perez said. "When you don't play every day, it's hard to keep your swing. I'm just trying to keep working so I'm ready when they need me."
Milton (4-3) allowed six hits and four runs in seven innings for his first loss after winning consecutive starts against the Cubs and St. Louis. He walked one and struck out five.
Milton retired the first 13 batters he faced before Matt Murton singled to right field with one out in the fifth inning. Jacque Jones and Cedeno followed with singles. Murton scored on Cedeno's hit and both runners moved up on Adam Dunn's throwing error, setting up Perez's sacrifice fly that gave Chicago a 2-0 lead.
David Ross cut the Reds' deficit to 2-1 in the bottom of the fifth with a solo homer to right-center field, his seventh of the season and second of the series.
Perez followed Milton's two-out walk to Cedeno in the seventh with a first-pitch homer to left to make it 4-1.
"Today was alright," said Milton, who hadn't allowed a walk in his previous three starts. "It just wasn't good enough. You can't let extra runners on base. That's something you can't do, but the mistake was the home run."
Phillips added his seventh homer of the season and second of the series with one out in the seventh, off reliever David Aardsma.
The Cubs broke the game open with a five-run eighth inning. Nevin started it with his 11th homer of the season and second since being acquired from Texas on May 31, and Cedeno added his own two-run shot, his second of the season.
"They just flat out beat us," Reds manager Jerry Narron said. "It's tough to win the game when you only have three hits going into the seventh inning."
Dunn hit his 20th homer in the eighth.
- Ryan Freel's start at third base was his first of the season. He also has started at second base and all three outfield positions.
- Marmol was the fourth Chicago pitcher to make his first major league start this season, the most for the Cubs since they had five in 2000.
- Murton is hitting .437 (7-for-16) in his career against Milton.
- Weathers left the game with what was diagnosed after the game as tendinitis in his right shoulder after giving up Nevin's homer and a single by Murton.
- The Cubs went 6-4 on their 10-game road trip, their longest of the season.
- Phillips' homer was the first allowed by Chicago relievers in 38 innings, dating back to Dunn's homer off Eyre on May 29.