Federer, who titled here from 2004-06, got the best of Ivan Ljubicic of Croatia in straight sets, while Nadal went the distance Wednesday to beat Australian Open runner-up Jo-Wilfried Tsonga on the hardcourts at the sprawling Indian Wells Tennis Garden.
Federer of Switzerland needed just over an hour to send Ljubicic packing, 6-3, 6-4, but the second-seeded Nadal needed just over three hours to stop the 17th-seeded Tsonga 6-7 (4-7), 7-6 (7-3), 7-5.
Nadal survived 12 aces from Tsonga, who also committed seven double faults in the setback. The French Tsonga lost to Serbian Novak Djokovic in January's Aussie Open finale.
The reigning three-time French Open champion and two-time Wimbledon runner-up Nadal managed one more service break (4-3) than did Tsonga on Day 7 here, including a key one to take a 6-5 lead in the third and final set. The Spaniard closed out the match on his serve after 3 hours, 3 minutes.
Nadal defeated Djokovic in last year's Indian Wells title bout.
Meanwhile, the eighth-seeded Blake blitzed Frenchman Richard Gasquet, 6-4, 6-2 and Djokovic, the third-seed here, easily dumped 16th-seeded Argentine Guillermo Canas in straight sets, 6-2, 6-3.
In other action, seventh-seeded Argentine David Nalbandian eased into the quarterfinals by dispatching 22nd-seeded former world No. 1 Spaniard Juan Carlos Ferrero 6-2, 6-2, and, in another fourth-round tilt, capable Swiss Stanislas Wawrinka snuck past Korean Hyung-Taik Lee 6-1, 5-7, 6-4.
There was also a pair of upsets on the day as unseeded German Tommy Haas stormed back from a set down to dispatch 11th-seeded Andy Murray of Great Britain, 2-6, 7-5, 6-3.
Also, American Mardy Fish outlasted two-time Indian Wells champ Lleyton Hewitt of Australia, 7-5, 3-6, 7-6 (7-4), in a match that lasted nearly 2 1/2 hours.