Lopez hit a tiebreaking RBI single in the 10th inning, helping the Mariners beat the Angels 2-1 on Sunday and snap an eight-game losing streak to the three-time defending AL West champions.
Vargas allowed one run and four hits through 7 2/3 innings, matching his longest outing of the season, and had a career-high nine strikeouts on the fifth anniversary of his first major league start.
"I had pretty good control of the changeup and I was able to get ahead with it and with my fastball. So there's definitely more potential for me to strike more people out," Vargas said. "But wins are the most important thing."
The left-hander has held the Angels to four earned runs over 21 innings in his three assignments against them this season. On May 9 at Anaheim, he yielded an unearned run over 7 1/3 innings in an 8-1 victory against Santana.
"Vargas is smart, and his changeup is pretty good," said Torii Hunter, who was 1 for 4 on his 35th birthday. "He uses it like 60-70 percent of the time, so you pretty much knew what you were going to get. You could sit on it, but you still couldn't hit it. He was using his fastball to set up his changeup and kept guys off-balance."
The Mariners' winning rally began when Ichiro Suzuki drew a leadoff walk from Kevin Jepsen (2-2) and advanced on Chone Figgins' sacrifice bunt. He then was caught in a rundown on Franklin Gutierrez's grounder to shortstop. Gutierrez stole second and scored when Lopez lined a 2-1 pitch to left field.
Brandon League (6-6) worked 1 1/3 scoreless innings for the victory after replacing Vargas, and David Aardsma got three outs for his 17th save in 21 attempts. He ended it by striking out Erick Aybar and Howie Kendrick with runners at first and second.
Hideki Matsui, the Angels' primary designated hitter, made his 15th start in left field and was 0 for 3. In the sixth inning, he called off Hunter -- a nine-time Gold Glove center fielder -- on a flyball by Gutierrez.
"He called me off in English -- loud, too," Hunter said with a laugh. "He kept yelling 'I got it! I got it!' So I just ran behind him and let him have it. I kept looking at him and I said: 'Man, go ahead. Take it!' I was scared of him, actually, because he's a big guy. We were cracking up and the whole bullpen was cracking up."
Santana allowed a run, three hits and four walks over seven innings and struck out seven. Over his last 14 starts, the Angels' offense had totaled 60 runs in his seven victories and just seven in the other seven outings.
"I hate that we don't come through for that guy and get runs, because he's been pitching his butt off," Hunter said.
Santana, whose teammates were no-hit through the first six innings in each of his previous two starts, was staked to a 1-0 lead in the second when Mike Napoli hit a first-pitch homer to left-center with two out for his 16th of the season. But Santana's wild pitch allowed Ryan Langerhans to score the tying run in the fifth.
"I've had a lot of at-bats against him, and I think today he had the best slider that I've ever seen him have. And he's always had good life on his fastball," Mariners shortstop Jack Wilson said.
The Angels had a great chance to regain the lead in the sixth after Kendrick led off with a triple to center field over Gutierrez's head. But Kendrick was unable to advance on Bobby Abreu's grounder to first with the infield in, and Vargas escaped the jam when Wilson snared Hunter's line drive on the lip of the grass before doubling up Kendrick -- who was halfway down the line.
"To be honest, I thought he scored on that ground ball by Abreu," Vargas said. "I was about to go into my windup to Hunter and Rob [catcher Rob Johnson] told me to look over there, and it surprised me. But I'm not even worried about him if he scores. If he does, he does. If he doesn't, he doesn't. I'm just trying to get the next guy out."
After the game the Angels placed LHP Scott Kazmir on the 15-day disabled list, retroactive to July 11, because of shoulder fatigue. Maicer Izturis was activated from the DL after missing 27 games with a left forearm strain, and backup 1B Paul McAnulty was designated for assignment. ... The Angels' staff has allowed six runs on wild pitches. ... Hunter is 2 for 17 with no RBIs since the All-Star break. The Mariners' pitching staff probably had something to do with it. Their starting rotation led the AL with a 3.55 ERA before the break, a franchise record for the first half of a season. ... Vargas was a college teammate of Angels RHP Jered Weaver at Long Beach State in 2004. ... Milton Bradley got picked off first base by Santana after drawing a leadoff walk in the second. ... Switch-hitter Chone Figgins, who left the Angels to sign a four-year, $36 million contract with the Mariners in December, was 1 for 15 in the series and is batting .228.