Trailing 7-3 in the third quarter, the Alouettes had moved from their own 37-yard line to Saskatchewan's 37 when Calvillo went down. He'd completed four of eight passes for 85 yards at the time of his injury.
Calvillo was replaced by Josh Neiswander, who saw his first regular-season action at QB with the Alouettes after signing with them in 2011.
Montreal's injured list continued to grow before halftime when Brandon London took a helmet-to-helmet hit from Roughriders safety Tyron Brackenridge.
Alouettes linebacker Kyries Hebert was sidelined on the same drive after he was kneed in the head by teammate Martin Bedard while covering a punt.
Saskatchewan wasn't immune to the injury bug either, as wide receiver Rob Bagg went down just before halftime after appearing to injure his left knee on a routine blocking assignment.
Bagg had season-ending surgery last year to repair a torn ACL in the same knee.