A victory would mean more than a series sweep for the Blue Jays as it would allow them to complete an umblemished home schedule against the Orioles this season at 10-0.
By clubbing four solo home runs in an 8-2 victory Tuesday night, the Blue Jays moved to 11-1 against the Orioles this season. The Orioles' only win over the Blue Jays this season was April 11 in the finale of a three-game series at Camden Yards.
The teams still have two more three-game series in Baltimore this season.
The Blue Jays already have clinched their first home series win since they swept the Orioles in three games July 20-22.
The Orioles will start right-hander David Hess (2-7, 5.95 ERA) on Wednesday while the Blue Jays will send out left-hander Thomas Pannone (0-0, 4.15), who will be making his first major league start.
Pannone made his major league debut Aug. 10 and has appeared in four games as a reliever.
Pannone started six games with Triple-A Buffalo this season and had a 4.91 ERA and 1.28 WHIP with 40 strikeouts in 36 2/3 innings. He has pitched in only nine minor league games this season, going 0-4 with a 5.36 ERA, including stints at Class A Dunedin and Double-A New Hampshire because of an 80-game suspension after testing positive for a performance-enhancing substance.
Hess made his major league debut May 12, winning two of his first three starts. He has not won since May 25, going 0-6 with a 6.61 ERA in 11 outings (nine starts) since his last win.
He received a no-decision in his only appearance against the Blue Jays, allowing one run in six innings of Baltimore's 5-4 loss at Toronto on June 7.
Kendrys Morales hit one of the Blue Jays' homers against the Orioles on Tuesday to add to the two he hit in the series opener on Monday. He has homered in three consecutive games for the third time in his career. The other two times were in 2016.
He also had an RBI single in going 3-for-4 on Tuesday.
Morales had overcome a poor start and now is batting .257 with 17 homers and 47 RBIs. He was slashing .188/.260/.312 on June 5.
"He's dangerous, he's always dangerous," Blue Jays manager John Gibbons said. "But he works hard, too. He's the first guy here just about every day, he spends his day in the cage. If anybody was going to come out of it, it was him."
Billy McKinney hit his first career home run for the Blue Jays.
Toronto center fielder Kevin Pillar was 1-for-4 with a double and has an eight-game hit streak, batting .419 with six doubles, one home run and eight RBIs during the streak.
The Blue Jays scored seven of their runs and hit three of their homers against Orioles starter Dylan Bundy. The Orioles also suffered defensive lapses behind him, making two errors.
"We've got to make some plays behind him," Orioles manager Buck Showalter said. "But his finish, the shape of his pitches, that's very unlike Dylan. This is probably the toughest stretch that he's had. It seems like every mistake he makes he's paying a price for it."
Cedric Mullins hit his second career homer for the Orioles in going 1-for-4 on Tuesday. He hit his first big-league homer on Saturday at Cleveland. He has reached base in 10 of his first 11 major league games since making his debut Aug. 10 and is batting .333 (13-for-39) with five doubles, two homers and four RBIs.