The Orioles traded Machado, who can be a free agent at the end of the season, to the Los Angeles Dodgers on Wednesday in a widely anticipated move.
Now the Orioles (28-69) and the Blue Jays (43-52) will resume their disappointing seasons at the Rogers Centre after the four-day All-Star break.
Baltimore will start right-hander Dylan Bundy (6-9, 4.35 ERA) in the opener against Toronto right-hander Sam Gaviglio (2-3, 4.58).
The Blue Jays entered the break having lost two in a row and seven of their past 10. The Orioles have won two in a row and four of their past 10.
Both team have fallen rapidly. In October 2016, the Blue Jays defeated the Orioles in the American League wild-card game at the Rogers Centre.
The Orioles are probably not finished trading yet as they look at a major rebuilding project and closer Zach Britton could the next star to depart.
The Blue Jays also are expected to be dealing before the July 31 deadline for trades without waivers with left-handed starter J.A. Happ the most likely to depart. Happ was their only All-Star and was credited with a save in the AL win on Tuesday.
Machado was the biggest prize on the market.
"Really, today is the start of a rebuilding process," Orioles executive vice president Dan Duquette said Wednesday. "We aim to retool our roster and get our organization back to the competitive stature that we've been used to."
In the deal for Machado, the Orioles received 21-year-old Cuban outfielder Yusniel Díaz, right-hander Dean Kremer, third baseman Rylan Bannon, right-handed reliever Zach Pop and second baseman Breyvic Valera.
Valera will report to Triple-A Norfolk. Diaz, Kremer, Bannon and Pop were assigned to Double-A Bowie.
Britton is returning to form after recovering from surgery to repair a ruptured Achilles that kept him out until mid-June.
"Clubs have become more interested in Zach as he has regained his velocity and particularly the sink and movement on his pitch," Duquette said. "He had a really good week this past week, so clubs have renewed their interest in Zach.
"We engaged other clubs on that front, but we're not as far down the road in the process, and I think that's partly because clubs were waiting to see how Zach was throwing, and exactly what role he could help on a pennant-contending team."
Among the other possible Orioles to be traded are such veterans as Brad Brach, Adam Jones, and Danny Valencia.
The Blue Jays already have traded Steve Pearce to the Boston Red Sox. They also could be entertaining offers for Josh Donaldson, Curtis Granderson, Marco Estrada, Tyler Clippard, Seunghwan Oh and John Axford.
Donaldson figured to be Toronto's biggest trading chip. He can become a free agent in the offseason but has not played much so far because of a calf injury and that could dampen interest.
Bundy will be looking for his first win in July on Friday. He is 0-2 with a 12.27 ERA in two starts for the month. He has done well in his career against Toronto, going 3-1 with a 1.17 ERA in eight games (four starts).
Gaviglio has never faced the Orioles. He will be looking for his first win since July 25 at Philadelphia. In nine starts since, he is 0-3 with a 5.44 ERA.
The Blue Jays will be without center fielder Kevin Pillar, who is expected to miss up to six weeks with a sternoclavicular joint injury suffered while making a diving catch on Saturday. Infielder Lourdes Gurriel Jr. was placed on the seven-day concussion disabled list after a collision at first base Saturday.