Federer, playing for the first time since his loss to Murray in the gold medal match at the London Olympics, breezed past Alex Bogomolov 6-3, 6-2. Currently ranked No. 1 in the world, Federer has won this tournament four times.
Djokovic, the defending champion and winner of the Masters event in Toronto last week, fought past Andreas Seppi 7-6 (7-4), 6-2. He lost to Murray in the finals here last year.
The Serbian superstar next faces s Nikolay Davydenko, who drubbed German Florian Mayer 6-3, 6-3 Wednesday.
Murray, the No. 3 seed, continued his recent hot streak with a 6-2, 6-4 rout of wild card Sam Querrey. In addition to his Olympic triumph, Murray recently reached the finals at Wimbledon before losing to Federer. He will next meet Jeremy Chardy, who bested Denis Istomin 6-4, 6-3.
No. 6 seed Juan Martin del Potro, the Olympic bronze medal winner, also reached the third round with a 7-5, 6-2 win over s Tommy Haas. The Argentine's next opponent will be s Viktor Troicki, who trounced Lleyton Hewitt 6-2, 6-0.
Also Wednesday, Mardy Fish posted a 6-3, 6-1 decision over Carlos Berlocq and No. 12 Marin Cilic breezed past qualifier Jesse Levine 7-5, 7-6 (8-6).
Radek Stepanek, Kei Nishikori and Milos Raonic also advanced Wednesday.