Raonic, who dropped Sunday's final in Montreal to Rafael Nadal, defeated Jack Sock 3-6, 6-4, 6-3 on Tuesday night to advance at the tournament just outside Cincinnati.
"Mentally I felt good, it was a bit about getting used to the conditions and the environment," Raonic said of his slow start against the American. "I stuck through it and in the second set I stayed positive and started to play a bit more aggressive.
The 12th seed from Thornhill, Ont., Raonic lost to Sock in Memphis in February after winning in San Jose the previous week for the third year running.
Raonic, now ranked a career-high 10th on the ATP Tour after beating Pospisil in the Rogers Cup semifinals, disposed of Sock in just under two hours. He will meet Serbia's Janko Tipsarevic in the next round.
"Tipsarevic will be a tough opponent," said Raonic. "I've got to keep doing what I've been doing, clean up my service games a bit and get better at closing it out."
Pospisil, now also ranked a career-best at No. 40, advanced when France's Gilles Simon retired with an injury.
Simon was trailing 6-3, 1-1 when he ended the match.
"It was a strange match," Pospisil said. "I started out well but I noticed that something was going on with him, I think it might have been the hip.
"It was difficult to play from that point. It was fortunate for me and unfortunate for him."
The Vernon, B.C., native needed just 36 minutes to sweep the opening set against Simon, who lost his fifth match in a row and hasn't won since mid-June.
Pospisil faces Belgium's David Goffin in the next round.
"The match will be tough and I don't see a clear favourite," Pospisil said. "He's a dangerous player, very talented, and has beaten some top players. We'll have to see."
Meanwhile, defending men's champion and fifth-seeded Roger Federer advanced to the third round with a 6-3, 7-6 (7) win over 29th-ranked Philipp Kohlschreiber.
"It was just really important to play somewhat of a clean match," said Federer, who already has won a record five W&S championships and improved to 7-0 in his career against Kohlschreiber. "Straight sets is always a good match. It's a good win for me."
John Isner defeated Florian Mayer 6-3, 6-4, and Grigor Dimitrov defeated Brian Baker 6-3, 6-2. Third-seeded David Ferrer edged Ryan Harrison 7-6 (5), 3-6, 6-4.
On the women's side, Maria Sharapova's return to WTA tournament play after more than a month away was short-lived following an upset loss to 17th-ranked American Sloane Stephens 2-6, 7-6 (5), 6-3.
In a match that lasted two hours 22 minutes, Stephens overcame double faults on two match points to pick up her first victory over Sharapova in four meetings.
"It definitely started out rough," Stephens said. "A set and 0-2, she was killing it. I'm glad I was able to turn it around and start playing good tennis."
Sharapova, the 2011 W&S champion and a 2010 finalist, showed no traces of the hip injury that had kept her sidelined since a second-round loss at Wimbledon.
"I thought I started the match off pretty well, but when you put yourself in a really good position, you can't let it go," Sharapova said. "That's what I did tonight. I didn't continue what I was doing well for the first set and a half, and that hurt me.
"You know, I stopped being patient. I started making a lot more errors, especially off the first ball — just errors that I shouldn't make. Obviously I haven't played in a long time, but I can't make that excuse for myself because I've got to be ready from the first match. So it's obviously disappointing, but that's the way it goes in this game."
Jimmy Connors, who won the tournament 41 years ago, watched from the stands in his first match as Sharapova's coach. She hired Connors, the 1972 champion and a 1986 finalist, in mid-July.
Fourteenth-seeded Jelena Jankovic, the 2009 champion and 2011 runner-up, advanced to the second round with a 7-6 (5), 5-7, 6-2 win over Wimbledon finalist Sabine Lisiski.
In earlier action, second-seeded Victoria Azarenka held off an upset bid by qualifier Vania King to pull out a 6-1, 7-6 (6) win and advance to the third round.
Azarenka rallied from a 3-0 deficit in the second set to force the tiebreaker against the 140th-ranked American.
Azarenka, who has been bothered by a lower back injury, won her first match since losing to Samantha Stosur in the finals of the Southern California Open two weeks ago.
"I think the beginning of the second set wasn't very good for me," Azarenka said. "There were quite a few unforced errors and just really fast mistakes, which didn't happen in the first set."
Varvara Lepchenko advanced with a 6-2, 2-6, 6-2 win over Flavia Pennetta, and Jamie Hampton needed three sets to overcome Anastasia Pavlyuchenkova 7-5, 4-6, 6-3.
Alize Cornet rallied past Ana Ivanovic 2-6, 7-6 (8), 6-4.
Sorana Cirstea, the 21st-ranked Romanian who lost to No. 1 Serena Williams in the finals of the Rogers Cup in Toronto on Sunday, withdrew from her first-round match against Yanina Wickmayer.
Cirstea was replaced by No. 43 Monica Niculescu, who lost in this past weekend's qualifying but stayed around in case a spot opened up in the singles main draw and to play doubles. The Romanian capitalized on her second chance with a 6-1, 6-2 win over the 58th-ranked Wickmayer.
No. 10 seed Caroline Wozniacki easily advanced with a 6-1, 6-1 win over Shuai Peng.