Guzman hit two home runs and Headley had another to hand Lincecum his latest setback, powering the Padres past the San Francisco Giants 6-3 on Wednesday to avoid a three-game sweep.
"He was aggressive with the fastball early and then he kind of got away from it a little bit," Padres outfielder Will Venable said. "And we were able to get a barrel on it."
Venable blooped a two-run double to help the Padres pound Lincecum (4-11), who allowed five runs in 4 2/3 innings. The two-time NL Cy Young Award winner had shown signs of progress in his previous two outings. Instead, he's still trying to piece three straight solid starts together and turnaround the worst season of his career.
"My stuff was pretty good in the beginning of the game," Lincecum said. "I started losing my spots more. I just have to execute those better and get a better result out of it."
Jason Marquis (4-5) gave up one run and three hits in 7 1/3 innings. He struck out eight and walked one to send the NL West-leading Giants to only their third loss in 12 games.
Huston Street extended his scoreless streak to 15 straight innings with a four-out save, including striking out All-Star Game MVP Melky Cabrera with two on to end the eighth. Street has converted all 16 save opportunities this season.
After allowing two runs in 15 innings over his previous two starts, Lincecum and the Giants were optimistic The Freak had finally snapped out of his funk.
So much for that.
Headley hammered a 1-1 fastball over the wall in center in the first to match his career-high of 12 home runs and give the Padres a 1-0 lead. It was the sixth home run allowed in the first inning this year by Lincecum, tying the mark he gave up all of last season.
The Giants answered back in the bottom of the inning when Gregor Blanco singled, stole second and eventually scored on Cabrera's fly out to left.
The run did little for Lincecum's confidence.
Lincecum loaded the bases in the fourth with one out. He struck out Marquis on three pitches and almost escaped until Venable's shallow two-run double landed in front of a diving Angel Pagan in left-center, putting the Padres ahead 3-1 and extending Lincecum's season-long slump.
"He's a foot away from getting out of the inning," Giants manager Bruce Bochy said.
San Francisco's shaggy-haired starter slumped around the mound, covering his face with his glove, never regaining his composure. Lincecum lofted a fastball clocked at 89 mph over the middle of the plate in the fifth that Guzman crushed over the wall in left.
Guzman also hit a solo shot off Brad Penny leading off the eighth for his sixth home run of the season to give San Diego a 6-1 lead.
After Lincecum walked John Baker, Bochy took that familiar trot to the mound to relieve his former ace before the sixth inning again. Lincecum left after giving up seven hits, five runs and three walks. He tossed 102 pitches -- 62 for strikes -- and struck out eight.
Lincecum now has a 5.88 ERA, the highest among any qualifying National League pitcher, and has only lasted six innings in nine of his 21 starts. The Giants are 6-15 this season when Lincecum takes the mound.
"Lincecum's got a good arm," Padres manager Bud Black said. "We got him today but he's never comfortable to face."
San Francisco's final effort to save Lincecum from another loss fell short.
Brandon Belt reached on a throwing error by shortstop Everth Cabrera that landed in the dugout to start the bottom of the eighth. Joaquin Arias singled home Belt and Theriot delivered an RBI single with two outs to slice San Diego's lead to 6-3.
Street entered and struck out Cabrera to end San Francisco's best shot.
Headley also hit 12 home runs in 2009. ... Giants 3B Pablo Sandoval sat out with a strained left hamstring he injured Tuesday night stretching for a catch to finish off a double play when he was at first base. The team will wait until Friday to decide whether he needs to be put on the disabled list. ... San Francisco's Hector Sanchez (sprained left knee) is scheduled to catch five innings for Triple-A Fresno on Thursday. Sanchez was put through catching and fielding drills Wednesday, including at first base. He's expected to come off the disabled list when eligible Aug. 2. ... Both teams are off Thursday. The Padres will play at Miami on Friday, while the Giants open a three-game series at home against the second-place Dodgers.