Federer, who won his fourth title here last year, lost just four points on serve, all in the first set.
Two of those were by double faults, and he never faced a break point and won 96 percent of his first serves.
Federer was done in 58 minutes, a contrast to the 2 hours, 23 minutes it took Lleyton Hewitt to upset No. 15 seed John Isner.
"I did what I could," Hewitt said. "I think I handled his serve pretty well and I made him hit a lot of balls.]
"I felt like I had more chances throughout the match. The first set could have gone either way and then I dug deep early in the second set to get up a break. That was a big momentum change."
The second of the two service breaks by Hewitt, in game seven of the third set, gave the 2002-03 champion a 4-3 lead. He added to it by holding serve for 5-3. Then, after Isner held for 5-4, Hewitt served out the match.
It didn't come easily, however. He got to 40-15 with a forehand pass, then lost three match points and fought off a break point before securing the win with a forehand down the line.
Kevin Anderson of South Africa ousted No. 4 seed David Ferrer of Spain 3-6, 6-4, 6-3.
In other matches, Benoit Paire of France beat No. 20 Philipp Kohlschreiber, Jarkko Nieminen of Finland topped No. 28 Fernando Verdasco, and Leonardo Mayer of Argentina eliminated No. 30 Mikhail Youzhny of Russia.
In women's matches, No. 7 seed Samantha Stosur earned a 6-3, 6-4 win over American wild card Madison Keys. Jamie Hampton of Auburn, Ala., upset 20th-seeded Hsieh Su-wei of Taiwan 6-3, 6-3.
Fourth-seeded Angelique Kerber defeated Irina-Camelia Begu of Romania 6-3, 6-2, and No. 10 seed Nadia Petrova of Russia beat Stefanie Voegele of Switzerland 6-2, 6-3.