Guerrero drove in three runs and Chone Figgins hit a three-run homer for the Angels, who received a fine pitching performance from John Lackey and got 13 hits in their most productive offensive showing of the season.
Guerrero hit solo homers in the first and seventh innings, and an RBI single in the fifth. The homers were his first extra-base hits since homering in his first at-bat on opening day.
"Every time I go up to the plate all I am looking for is to make solid contact. That will never change regardless of whether I have one home run or no home runs," Guerrero said through an interpreter. "I never go up looking for the home run."
Lopez was merely looking for a home-run call when he sent a drive to center in the second inning with Miguel Tejada on first base.
As the ball approached the 7-foot wall, Darin Erstad leaped to make the catch. When he tumbled to the ground, it was uncertain whether he caught the ball.
By the time Erstad displayed his empty glove, Tejada had retreated from second base and was passed by Lopez. By rule, Lopez was credited with an RBI single and called out for passing the runner.
"Me and Tejada were looking at the umpire the whole time, wondering what kind of call he was going to make. We were wondering if the ball was out or (Erstad) got it in his glove," Lopez said. "One umpire called an out, so obviously Tejada went back to first base. Then the other umpire said the ball was out. But by the time he made the call, I had already passed Tejada."
The Orioles might have survived that mistake, but they also misplayed a double steal in the next inning, allowing Maicer Izturis to steal home and give the Angels a lead they would not lose.
With runners at the corners and Adam Kennedy at the plate, Figgins got caught in a rundown while trying to steal second. Izturis broke for the plate and beat the throw from first baseman Jeff Conine while Figgins took second.
"We made a couple of mistakes that cost us," Orioles manager Sam Perlozzo said. "We could have come out of that five innings up 3-2 or 4-2 and it would have been a whole different ballgame. But it unraveled after that."
Lackey (2-1) allowed two runs and six hits in eight innings. He struck out five and walked none.
"John Lackey is probably the biggest story. He was terrific for eight innings," Angels manager Mike Scioscia said.
Conine homered for the Orioles, whose three-game winning streak ended.
Orioles starter Kris Benson (1-2) gave up four runs and nine hits in five innings. The right-hander came in with a 1.93 ERA, but yielded at least one hit in every inning.
His wife, model Anna Benson, was among the 19,904 in attendance. It was the second time she's seen Kris pitch since he came to the Orioles in an offseason trade with the New York Mets.
"I was in Tampa, but it's my first time in Camden Yards," she said. "I'm just here with him. Any time he pitches, I'll be here."
Guerrero sent a 2-1 fastball into the left-field seats to give Los Angeles a 1-0 lead.
Baltimore tied it in the second, but was left aching for more after Tejada and Lopez inadvertently crossed paths.
Los Angeles made it 4-1 with a two-run fifth. Izturis doubled and scored on a double by Kennedy, who came home on a broken-bat single by Guerrero.
Conine hit his 200th career homer in the bottom half, an opposite-field solo shot to right.
Guerrero homered off Sendy Rleal in the seventh, and the Angels pulled away with a four-run eighth, capped by Figgins' homer.
- Angels DH Tim Salmon left in the fourth inning with an injury. "His groin got a little bit tight. That'll be day to day," Scioscia said.
- Conine has three hits this season: two homers and an RBI double.
- Los Angeles has scored in the first inning in eight of its 12 games.