The Blue Jays appeared to have the series won Wednesday night when they took a 3-1 lead into the ninth inning but suffered a 5-4 loss.
The teams have split the first two games.
Toronto reliever Tyler Clippard, trying for his third save of the season, allowed three walks and a pair of two-run singles, including one by Shohei Ohtani, to give the Angels a 5-3 lead.
The Blue Jays could score only once in the bottom of the ninth despite opening the inning with two singles and a double.
"I don't overreact on one game, it was a tough game, it was an ugly game," Toronto manager John Gibbons said. "Those guys (the bullpen) have been great all year and they'll bounce back."
The Angels will start right-hander Nick Tropeano (1-3, 4.45 ERA) against Blue Jays right-hander Marco Estrada (2-4, 5.15).
The Blue Jays have not won a home series since April 17-18 against the Kansas City Royals, a three-game sweep that included a doubleheader when Toronto totaled 31 runs.
The Blue Jays (23-26) have lost nine of their past 12 games and dropped seven of their past eight home games. They have yet to win back-to-back games in May and are 7-14 for the month.
The Angels (27-22) are 15-5 on the road this season, the highest road winning percentage (.750) in the majors. They have won two of three games after a five-game losing streak.
Andrelton Simmons, whose two-run single in the ninth put Los Angeles into a 5-3 lead on Wednesday, enjoys hitting at the Rogers Centre. In 13 career games there, he is batting .364 (20-for-55) with four doubles, a triple and 10 RBIs.
Tropeano will be making his seventh start of the season for the Angeles and this third on the road. It will be his first career start against the Blue Jays.
This will be Tropeano's third start since come back from the disabled list (right shoulder inflammation).
Tropeano took the loss Friday against the Tampa Bay Rays when he allowed four earned runs on six hits in 2 2/3 innings.
In his two road starts this season, he is 1-1 with a 3.00 ERA.
Estrada is 1-1 with a 6.62 ERA in three career starts against the Angels. He will be looking for his first win since April 20, a span of five starts. He is 0-3 with a 5.02 ERA in those starts, but the team is 2-3.
The Angels appeared to have squandered their chances to win the game before Clippard let them grab the lead in the ninth. Los Angeles had stranded 11 runners over the first eight innings and 13 for the whole game.
"We did a lot of good things at the plate," Angels manager Mike Scioscia said. "We had a lot of chances, but we couldn't get that key hit at some point and a couple of rough decisions on the base paths. For the most part, guys kept playing, guys kept plugging away. We did force the action, we stole some bags."
The four-run ninth was their highest in a ninth inning since they also scored four on May 5, 2017, against the Houston Astros.
The Blue Jays' loss was their first in 18 games this season when leading after eight innings.