Both players had been giant-killers throughout the week, Makarova taking out No.2 seed Petra Kvitova and Vandeweghe, who actually came through the qualies, defeating No.9 seed Ana Ivanovic and No.7 seed Jelena Jankovic, the first time she has ever beaten two Top 10 players at the same tournament.
And when the two finally came to blows it was Makarova who came out faster, storming through the first set, 6-1, and looking like she might move on in straights as she inched ahead 3-2 in the second.
Vandeweghe came alive at that point, starting to find the mark on her big serve and groundstrokes and completely taking it to Makarova, winning four of the next five games to take the second set, 6-4.
But the momentum shift was short-lived, as Makarova won 12 of the first 13 points of the third to build a 3-0 lead and she eventually held at love to run away with the set and the match, 6-1, 4-6, 6-1.
"She's in really good shape now and hitting so hard - she's so aggressive, and serving really well too," Makarova said afterwards. "It was really tough to stay calm and solid. I just tried to keep playing my game, and I think I did it well in the first and third set, and I'm happy I could come through.
"I think today was just about the concentration and who could be more aggressive."
Makarova is now through to the biggest semifinal of her career. She has been to one semifinal at the Premier level or higher before, going all the way to the title in Eastbourne in 2010, but that was a regular Premier event with $600,000 in prize money - this is a Premier 5 event with $2,440,070.
"I'm really enjoying being in Montréal, and spending time with my mom. I came quite late from Washington so I didn't have a lot of time to just walk around or do something else, because I'm just playing every day - I'm playing doubles and singles, so it's quite a busy schedule this week.
"But I'm really enjoying it here. I'm really happy."
Up next for Makarova is the No.3 seed, Agnieszka Radwanska, who won her quarterfinal match at night. Radwanska leads Makarova in their head-to-head, 3-2, though she has lost their last two.
"She's playing really smart, and she's using the power of her opponents well," Makarova said.
"Against her the key is definitely to be as aggressive as you can be."