Ohtani (11-8) allowed two hits - a single for George Springer in the first, and a two-out double for Vladimir Guerrero Jr. in the third - in his career-best 11th win. David Fletcher had three hits and scored the winning run on Luis Rengifo's single in the sixth.
Jimmy Herget finished the two-hitter as the Angels won consecutive games after losing the previous six, blanking the Blue Jays for the second day in a row.
Los Angeles, which won 12-0 Friday, recorded its AL-best 16th shutout.
Toronto wasted a strong performance by All-Star right-hander Alek Manoah (12-7), who struck out eight in seven innings.
Velazquez hit his eighth homer against Anthony Bass in the ninth. He also went deep on Friday.
Ohtani threw a season-high 109 pitches, 72 for strikes, in his first win since Aug. 9 at Oakland. He lowered his ERA to 2.67.
Herget retired all six batters he faced for his third save in four chances.
At the plate, Ohtani walked in the first, struck out in the fourth and reached on a fielder's choice in the sixth.
While awaiting a 3-2 pitch from right-hander Yimi Garcia in the eighth, Ohtani asked for time and backed out of the box. Umpire Shane Livensparger didn't grant the request but Garcia's pitch missed high, giving Ohtani his second walk.
Already upset at Ohtani's walk, interim Blue Jays manager John Schneider was ejected for arguing with Livensparger after Garcia walked the next batter, Mike Ford, on five pitches. The ejection was Schneider's first.
Manoah cruised through five innings before running into trouble in the sixth.
Fletcher led off with a single and Mike Trout walked before Ohtani beat out a potential double-play grounder, with the call at first base overturned on replay. Rengifo drove in Fletcher with a first-pitch single to left.
Springer started in center field for the first time since being activated off the injured list Aug. 15. Springer's sore right elbow had limited him to DH duties since returning.
Springer singled in his first at-bat, extending his season-long hitting streak to 11.
THIRTY YEARS SINCE 1992
The Blue Jays honored their 1992 World Series championship team during a pregame ceremony. Among the former players, staff and executives on hand were Dave Winfield, Dave Stieb, Todd Stottlemyre, Duane Ward, Candy Maldonado, Juan Guzman, World Series MVP Pat Borders and manager Cito Gaston.
In lieu of a ceremonial first pitch, slugger Joe Carter and pitcher Mike Timlin recreated the final out of Toronto's extra-inning Game 6 win in Atlanta, which came when Timlin fielded Otis Nixon's bunt to the mound and tossed to Carter at first.
Ohtani threw 108 pitches in back-to-back home starts in June, both wins. He beat Kansas City on June 22 and the White Sox on June 29.
Angels outfielder Ryan Aguilar got his first career hit in the fifth, a double to right, but Blue Jays outfielder Jackie Bradley Jr. threw Aguilar out at third base by a wide margin.
Blue Jays: OF Teoscar Hernandez (left foot) did not start. Hernandez fouled a ball off his foot in the first inning Friday and left the game in the third.
Angels left-hander Tucker Davidson (2-4, 6.23 ERA) starts Sunday's series finale against Blue Jays righty Ross Stripling (6-3, 2.84 ERA). Stripling has allowed two earned runs or fewer in six straight starts.
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