Berdych, seeking his 10th career ATP title and first on US soil, defeated US qualifier Robby Ginepri 6-1, 6-4 on Wednesday 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.
Berdych connected on only 48 percent of his first serves but still needed only 68 minutes to dispatch Ginepri, whose only two ATP wins this year came in the past 10 days, and book a third-round date with Canada's Vasek Pospisil.
"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."
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.
"Felt good and didn't feel so good," Raonic said. "You have to understand yourself and not expect to play your best tennis."
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.
"I just played two fairly solid tie-breakers," Raonic said. "I made the most of my opportunities on the important points. I was able to tough that one through."
Isner, twice a Washington runner-up, was coming off a title last week in Atlanta. He double-faulted for the third and final time on the penultimate point to help Johnson win their first meeting.
- Nishikori fights through -
Nishikori, seeking his sixth career title and third of the year, fired nine aces against 12 by Querrey in advancing after one hour and 52 minutes.
"I stayed solid from the baseline and concentrated on my service games," Nishikori said. "It was a good finish. There were some tight moments but I'm very happy with the way I'm playing."
Nishikori next faces Slovakian Lukas Lacko with sixth seed Richard Gasquet a potential quarter-final foe after the Frenchman beat Israel's Dudi Sela 6-3, 6-2.
Dominican Victor Estrella Burgos upset Spanish eighth seed Feliciano Lopez 7-6 (7/5), 6-4. He meets Colombian Santiago Giraldo next.
On the women's side, Japan's Kurumi Nara was leading 3-6, 6-2, 4-0 when Zarina Diyas of Kazakhstan retired with a right elbow injury.
Nara reached a quarter-final against France's Kristina Mladenovic, who followed up an upset of Czech top seed Lucie Safarova with a 6-3, 6-4 victory over US qualifier Taylor Townsend.
New Zealand's Marina Erakovic beat American Shelby Rogers 6-2, 6-2, and will next face Serbian Bojana Jovanovski, who ousted Romanian eighth seed Sorana Cirstea 4-6, 7-5, 6-3.