Berdych, seeking his 10th career ATP title and first on US soil, defeated US qualifier Robby Ginepri 6-1, 6-4 at the $1.9 million (1.4m euro) hardcourt tune-up for the US Open.
Canadian second seed Raonic fired 16 aces in ousting American Jack Sock 7-6 (7/3), 7-6 (7/3) while American Steve Johnson never faced a break point and withstood a 29-ace barrage to defeat countryman Isner 6-7 (5/7), 6-3, 7-6 (8/6).
And Japan's fourth-seeded Kei Nishikori outlasted American Sam Querrey 6-4, 5-7, 6-4 to join them in the last 16.
"I felt good on the court," Berdych said. "My goal was from the first point try to be focused. It can be tougher after you have a few weeks off."
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Raonic, coming off a loss to Roger Federer in his first Grand Slam semi-final, advanced to a third-round match with 33-year-old Australian Lleyton Hewitt, the 2001 US Open and 2002 Wimbledon champion.
Sock seized a 3-1 edge in the first tie-breaker but Raonic answered by winning the next six points to claim the opening set, the last coming when Sock netted a forehand.
"I'm hahappy was able to come back," Raonic said.
Sock served for the second set in the 10th game but Raonic broke back and reached another tie-breaker that went to 3-3. Raonic swept the next four points, the last on a forehand winner for the victory in one hour 42 minutes.