"Jeff and Ervin, they were on a roll today," Angels manager Mike Scioscia said. "They really had good chemistry. It makes it a little easier when you're trying to put pitches together when a guy has the command that Ervin did today. He knew what he wanted to do and he did it."
Mathis figured Santana shook him off fewer than five times all game.
"He was nice and smooth today, he was hitting his spots and throwing his slider and his changeup for strikes," Mathis said. "When he's feeling all three pitches, it's fun back there."
Hideki Matsui went 2 for 4 with two doubles and an RBI as Los Angeles improved to 6-7 after opening the season with six losses in eight games. The Angels swept a three-game series in Toronto for the first time since July 9-11, 2004.
"We've got to keep passing that baton and keep going," Santana said.
Santana (1-2) entered with a 6.94 ERA in two starts but was dominant against the Blue Jays, setting down 17 in a row before Adam Lind homered to right on a 3-2 pitch with two outs in the ninth, his third. The next batter, Vernon Wells, ended it with a fly to center.
"Today everything was working how I wanted," Santana said. "Location was the main thing for me today."
Santana allowed four hits, walked none and struck out six. He needed just five pitches to retire the side in the sixth.
The only blemish was the changeup that Lind homered on in the ninth, the ninth pitch of the at bat.
"It wasn't a bad pitch," Mathis said. "[Lind] just went down and got it."
Toronto left-hander Ricky Romero, who took a no-hitter into the eighth in his last start, didn't give up a hit through the first three innings in this one, but allowed the leadoff man to reach safely in the fourth, fifth and sixth.
Romero escaped the first two times but paid the price after Erick Aybar doubled to lead off the sixth, then scored two outs later when Matsui doubled to center.
"I got to watch him in the playoffs," Mathis said of Matsui. "The man can hit. He's fun to watch. It's just nice to have him on our side now."
Romero (1-1) allowed one run and five hits in eight innings. He walked two and struck out six.
"Either one of those guys deserved to win today and fortunately we got it done," Scioscia said.
Matsui doubled to begin the ninth against Scott Downs and was replaced by pinch-runner Mike Napoli. Kendry Morales followed with a hard grounder that went through the legs of first baseman Lyle Overbay, scoring Napoli.
Morales took second on the throw to the plate and scored when Mathis followed with a double, extending his hitting streak to a career-high nine games.
Outfielder Fred Lewis made his first start since joining Toronto in Thursday's trade with San Francisco. Lewis hit a two-out double in the third and stole third, but was left stranded when Alex Gonzalez struck out.
One day after snapping an 0 for 18 slump, Overbay went 0 for 3, dropping his average to .080.
As they signed autographs on the field at a season ticket holder's BBQ following the game, Wells, Dana Eveland, Casey Janssen, Shaun Marcum and Romero all wore Overbay jerseys in support of their struggling teammate.
Angels OF Torii Hunter got the day off after complaining of soreness following two games on the artificial turf. Reggie Willits started in center. ... Los Angeles LHP Brian Fuentes (back) will pitch one inning, or throw 20-25 pitches, for Class-A Rancho Cucamonga on Monday and could rejoin the Angels on Wednesday. ... Toronto 3B Edwin Encarnacion (sore right arm) missed his fourth straight game. ... Attendance was 14,246.