The 429-foot blast, his 14th of the season, ended a 15-inning scoring drought at the hands of the Yankees.
Grilli replaced Biagini in the eighth and allowed Gardner's 12th homer to lead off the inning and Holliday's 12th with two out followed by Castro's ninth and Gregorius' fourth.
But for Gardner, the eighth-inning power surge wasn't the most significant part of the day.
NY went 3-4 on its seven-game trip, failing to win consecutive games.
In eight at-bats against Grilli this season, they have five home runs and a double.
"His stuff wasn't sharp, his location wasn't good", Yankees manager Joe Girardi said. They eked out three hits (and three total bases) in addition to five walks. And while the Blue Jays as a collective weren't at their best Saturday, Biagini did have himself a very fine day in only his sixth start at the major-league level. He declined to speak to reporters following the game.
Moving ahead to the bottom of the third, Justin Smoak came up to the plate again looking to provide even further damage and did just that as he drove in Jose Bautista from third base on a sacrifice fly.
The Yankees are in Toronto (they won 12-2 on Thursday), but this baseball may not be.
"We had three pitches today that we could work with and the changeup was really good", Sabathia said. Kendrys Morales strikes out swinging.
Yankees: LHP Jordan Montgomery (2-4, 4.11) lasted just 4 1/3 innings at Baltimore on May 29, the shortest of his nine big league starts.
"But I am getting a few pitches to hit as of late and I haven't missed them", said the 2015 AL MVP who was activated from the DL last week.
Adam Warren, Tyler Clippard and Dellin Betances each pitched a hitless innings in relief. Severino is 0-3 with a 6.38 ERA in six appearances (five starts) versus Toronto, including a 7-1 loss May 1 when he permitted five runs and eight hits in 5 2/3 innings.
"We didn't score him any runs, obviously, but he had it all working", Gibbons said.
Hicks and Judge each extended their hitting streaks to seven games with the doubles. Biagini set down 10 straight before Castro and Gregorius doubled in the seventh.
Toronto put runners at first and second in the second, third and fifth innings but came up empty each time.
Toronto Blue Jays starting pitcher Marcus Stroman (6) throws a pitch at the Rogers Centre.
Robinson Cano, Curtis Granderson, Russell Martin, and Mark Teixeira were the four Yankees who homered in the same inning against the Red Sox in 2012.
Yankees: OF Jacoby Ellsbury (concussion) has been shut down after suffering headaches and will visit a neurologist when the team returns home Monday.
On Tuesday, J.A. Happ, a 20-game victor a year ago, returned to the lineup against the Cincinnati Reds after more than a month on the shelf with a sore left elbow.
Blue Jays fourth. Luke Maile singles to center field. With Danny Barnes in, Holliday walked and Castro followed with a two-run homer. The neck is improving and the Blue Jays are hoping to avoid putting Martin on the disabled list.
The four home runs in the eighth - all against Jason Grilli - were the most ever allowed in one inning by a Blue Jays reliever.
The back-to-back-to-back home runs capped off a four-run eighth inning and secured a 7-0 victory for NY on the road.
After going 3-for-52 in his first 18 games with the Blue Jays, the 26-year-old has hits in three consecutive contests including a two-run home run on Wednesday.
Will the Yankees pull off the upset this afternoon in Toronto when they take on the Blue Jays at 1:07PM ET?