The Burnaby, B.C., native was declared the winner over Nikolay Davydenko at Uniprix Stadium after his Russian opponent withdrew after three games, trailing 3-0, due to an unspecified injury.
Pospisil, 23, is the first Canadian in the semifinals since Mike Belkin in 1969. The last Canadian to win the tournament, then called the Canadian Open, was Robert Bedard in 1958.
He'll play the winner of the afternoon quarter-final between fellow Canadian Milos Raonic and Latvia's Ernests Gulbis.
Pospisil has posted some impressive victories this week. The wild-card entry upset American John Isner in the opening round and then topped Czech veteran Radek Stepanek.
The 71st-ranked Pospisil followed that up with a stunner on Thursday when he knocked off fifth-seeded Tomas Berdych of the Czech Republic. It was the Canadian's first-ever victory over a top-10 player.
Davydenko has been ranked as high as No. 3 in the world but currently holds the No. 47 position.
The semifinals are scheduled for Saturday and the final is set for Sunday at the US$3.49-million hardcourt event.