Cleveland manager Manny Acta was satisfied with the road trip despite the fact that the Indians lost two of three to a team that was 0 for 12 with runners in scoring position in the series.
"I'll take 4-2 on the West Coast anytime," Acta said. "Today we had very good pitching. I can't say enough about our pitching staff to far. They took us all the way to the 12th inning today, because we didn't execute offensively. And that kept us from a victory."
Wells singled sharply into the hole off the glove of shortstop Asdrubal Cabrera with one out in the 12th, only his fifth hit in 49 at-bats this season. Chad Durbin (0-1) walked Alberto Callaspo, and both runners advanced on a wild pitch to Mark Trumbo.
"There's no need to put a guy into scoring position. You have to make them hit the guy there," Durbin said. "Making them hit a ground ball was all I was thinking. I kept trying to throw sinkers middle-away and let it run off the plate or down, but I wasn't very efficient. I wasn't being aggressive over the plate. That's what a reliever has to do — attack the zone."
An intentional walk to Trumbo loaded the bases for Mathis, who hit a fly to medium center field and Wells streaked home ahead of Michael Brantley's throw. Last September at Anaheim, Mathis beat the Indians by the same 4-3 score in the 16th inning with a sacrifice fly.
"We just played a hot team, and they won eight in a row before yesterday. So just to cool those guys down shows that we're playing pretty well ourselves," Hunter said.
Hisanori Takahashi (1-0) got his first AL victory with two perfect innings. The left-hander was 10-6 with the Mets last season as a rookie with 3.61 ERA in 53 appearances, including 12 starts.
Angels right-hander Ervin Santana, still looking for his first win of the season, gave up three runs and six hits over seven-plus innings and struck out three.
Santana, who has spent his entire seven-year career with the Angels and defeated every American League team except Cleveland, entered the eighth with a 3-2 lead and departed after giving up a leadoff single to Adam Everett.
Brantley greeted Scott Downs with a single that sent Everett to third. Everett was caught in a rundown and tagged out by third baseman Callaspo after he fielded Cabrera's grounder.
Brantley and Cabrera both advanced on Downs' wild pitch, and Brantley scored the tying run on a groundout by Shin-Soo Choo before Fernando Rodney came in and struck out Carlos Santana looking. The blown save by Downs left Ervin Santana's career record against the Indians at 0-6 with a 4.98 ERA.
"He has great life on his fastball, a great sinker and a slider that he can throw for strikes anytime he wants," said Orlando Cabrera, who played for the Angels during Santana's first three seasons in the majors. "When you have the stuff that Ervin has, it was just a matter of him staying healthy. I've been watching him on TV, and he's become a pitcher, not a thrower, and he's got a great team behind him that can make good plays defensively."
Cleveland had runners at the corners with one out in the fourth, but Santana escaped the jam on a double-play grounder by Orlando Cabrera, whose comebacker deflected off the pitcher's glove to second baseman Howie Kendrick.
The Angels got three in the bottom half against Carlos Carrasco for a 3-1 lead. Kendrick led off with a double in the gap and circled the bases on a throwing error to second base by Asdrubal Cabrera, who was in short left field along with second baseman Orlando Cabrera for the cutoff throw as first baseman Matt LaPorta hustled over to cover the bag.
Bobby Abreu then drew his sixth walk of the three-game series and Torii Hunter drove an 0-1 pitch over the wall in left-center, the 15th homer by the Angels this season and only the second with anyone on base.
"He just hung a slider. I saw it, my radar went off and I was able to put something on it," Hunter said.
Cleveland got a run back in the fifth when Everett beat out a two-out single to deep shortstop and scored on Brantley's double high off the 18-foot wall in right field.
Carrasco allowed three runs and five hits over seven innings with five strikeouts and two walks.
"Carrasco threw a tremendous ballgame and had a very live fastball," Acta said. "I don't think he gave up anything on the fastball. The home run came was on a slider and Kendrick's double was on a breaking ball."
NOTES: Indians RHP Joe Smith, who began the season on the 15-day disabled list because of a strained abdominal muscle, is expected to be activated on Friday for the opener of a three-game series at home against Baltimore. CF Grady Sizemore and INF-DH Jason Donald, who have been on rehab assignments with Double-A Akron, will join Triple-A Columbus on Thursday for a game at Toledo. ... Angels relievers have not been charged with a run in 22 innings over their last seven games, after giving up 14 runs and six homers in 18 1-3 innings during the team's first five games of the season.