Pospisil, who at 36th in the rankings was 31 spots beneath Berdych, collected his third career victory over a top-10 foe, his first coming over Berdych nearly a year ago in the round of 16 at Canada.
"That was not one of my best," Berdych said on Thursday. "It's something that needs to be dealt with and go on. I need to move on and work even harder."
In the quarter-finals for the second week in a row at a US Open hardcourt warm-up event, Pospisil will face Santiago Giraldo, who beat Victor Estrella Burgos 6-2, 6-0.
"It was a huge win for me," Pospisil said. "Beating (Berdych) last year gave me a little more confidence."
Pospisil, who joined American Jack Sock in winning the Wimbledon doubles crown, seeks his second semi-final of the season after a back injury contributed to his going winless in eight matches from February to May.
"If I'm serving well and moving well, I know I can give these guys a lot of trouble," Pospisil said.
Wimbledon semi-finalist Milos Raonic fired 27 aces in a 7-6 (7/1), 7-6 (7/3) victory over Australian Lleyton Hewitt that put the second-seeded Canadian in the quarter-finals.
"I did a lot of good things, especially the way I fought through the important games," Raonic said. "In those key moments, my attitude got me through."
Raonic, who also won his opener over Sock in two tie-breakers, will face US giant-killer Steve Johnson for a spot in the last four.
Johnson dumped ATP aces leader Ivo Karlovic 3-6, 7-6 (7/4), 7-6 (9/7) despite 27 aces by the Croatian ninth seed. A day earlier he beat US fifth seed John Isner, who ranks second in aces and fired 29 past Johnson.
"He couldn't have had any better preparation to face me," said Raonic, who ranks third in ATP aces. "It's going to be very difficult.
"Compared to the previous two he got, I think I control the center of the court and move a little better. Hopefully that will get me through."
In each win, Johnson benefitted from a double fault by his rival on the penultimate point to win a third-set tie-breaker.
"I can learn a lot from a match like this and take it into the next match," Johnson said.
Japanese fourth seed Kei Nishikori and French sixth seed Richard Gasquet, the top men's seeds remaining after Raonic, will meet in another quarter-final.
Nishikori dispatched Slovakian Lukas Lacko 6-2, 2-6, 6-3, after being pushed to three sets for a second straight day.
- Gasquet doing OK -
Gasquet, coming off a right arm injury that saw him withdraw last week at Atlanta, beat American Tim Smyczek 6-3, 6-2.
"I couldn't even serve a ball," Gasquet said. "For three days I didn't serve. Now I'm very sound. I feel no pain. It feels fine."
South African seventh seed Kevin Anderson downed Tunisia's Malek Jaziri 6-3, 6-4. He next plays US left-hander Donald Young, who outlasted Uzbek Denis Istomin 6-3, 3-6, 6-3.
Young is on a three-match win streak for the first time since a run to his only ATP final in 2011 at Bangkok, where he lost to Britain's Andy Murray.
"I'm excited about it," Young said. "I had to fight some nerves. I'm happy to get through. It's a big win for me."
Russians Ekaterina Makarova and Anastasia Pavlyuchenkova, the top remaining women's seeds, will meet in a quarter-final.
Second-seeded Makarova beat American Lauren Davis 6-2, 6-4 and fifth-seeded Pavlyuchenkova defeated Japanese qualifier Hiroko Kuwata 6-3, 6-3.
Russian sixth seed Svetlana Kuznetsova, twice a Grand Slam champion, ousted Belgium's Kirsten Flipkens 6-4, 7-5 to book a last-eight date with American Vania King.
- Sports & Recreation
- Tomas Berdych
- Vasek Pospisil
- Milos Raonic