The Czech's superior all-round game was clear on Court Suzanne Lenglen as he dominated throughout.
Berdych built a winning platform by breaking the 10th seed in his first service game in each of the first two sets, both of which lasted 34 minutes.
In the third set, Isner delayed the crucial break until his second service game but Berdych was never troubled as he moved through to the quarter-finals where he will be waiting for either 17-times grand slam champion Roger Federer or Ernests Gulbis who play later.
Isner was the last man from the United States left in the draw.
Results from the French Open round three
24-Fernando Verdasco (Spain) beat 12-Richard Gasquet (France) 6-3 6-2 6-3
- Sports & Recreation
- Court Suzanne Lenglen