Guthrie (6-3) allowed two hits in seven innings, struck out six and walked three. His ERA dropped to 2.88, third in the AL behind Oakland's Dan Haren (2.41) and Minnesota's Johan Santana (2.65).
"The guy is a winner in every sense of the word," Orioles manager Dave Trembley said. "What he does is prepare the same way every time out. He has poise, and he doesn't get rattled. He keeps coming at you. He was dominant."
Guthrie won consecutive starts for the first time in the major leagues as he improved to 5-0 in eight starts on the road.
Chad Bradford pitched the eighth and Jamie Walker finished for his first save since July 21, 2004, for Detroit against Kansas City. The A's have been shut out eight times, tied with Chicago and Minnesota for the AL lead.
Orioles closer Chris Ray informed Trembley of some stiffness before the game and was unavailable to pitch.
"I'm not a closer by any means, but it worked out today," Walker said.
Oakland's Dallas Braden (1-5) gave up three hits and four walks in seven innings, his longest outing in his six major league starts. He has lost five straight decisions, the longest skid by an A's pitcher since Joe Kennedy dropped five in a row in 2005.
"The last time was a learning process," he said, referring to a 4-1 loss to Texas. "This was a little better than the last time."
The A's have lost 11 of 13, falling 11½ games behind the AL West-leading Angels.
Guthrie, a Stanford product claimed on waivers from Cleveland during the offseason, was a first-round draft pick in 2002. He retired 10 of 11 hitters at one point and never faced more than four hitters in an inning.
"Since the start of the 2005 season everything started clicking for me and I've been building on that every since," Guthrie said. "I was consciously trying to use my fastball more. It felt pretty sharp. I got tired in the sixth and seventh and had to battle through that but I had good location and that's what got us through."
Guthrie, who did not have a decision in 16 major league appearances before this season, did not allow a hit after Travis Buck's two-out single in the third. Only five of his 21 outs were recorded in the outfield.
"He was one of those guys that wasn't leaving anything over the middle of the plate," Oakland's Nick Swisher said. "It wasn't like we were chasing anything, he just hit his spots."
"I thought we were going to break it open in the first inning," Trembley said. "Give Braden credit; he made good pitches. Guthrie backed us up though and gave us a lift with the way he pitched."
Payton singled off Andrew Brown in the ninth after Markakis singled and stole second.
- Patterson singled in the first inning for the fifth consecutive game, extending his hitting streak to 10 games.
- Swisher walked in his first at bat and has 68, tied with Jim Thome for second in the AL.
- A's 2B Mark Ellis extended his errorless streak to 57 games, one off his career high.
- Guthrie stopped a streak of six games in which he allowed a home run.
- Braden recorded his first major league pickoff when he caught Markakis off first base in the fourth.