Djokovic, who won in Miami last year and in 2007, cruised into the third round with 6-4, 6-4 win over Cypriot Marcos Baghdatis.
Meanwhile, two-time Miami champ Federer survived a second-set tiebreaker and advanced by downing American wild card Ryan Harrison 6-2, 7-6 (7-3).
With the win, the Swiss former world No. 1 moved on to face Roddick. The American fired 10 aces Saturday while breezing past Luxembourger Gillies Muller 6-3, 6-2 in 73 minutes.
No. 8 seed Mardy Fish of the United States prevailed over Canadian Frank Dancevic 6-3, 7-6 (7-1), while No. 11 Juan Martin Del Potro of Argentina downed Croatia's Ivo Karlovic 7-5, 6-4.
Among the other winners at Miami Saturday were Albert Ramos of Spain, France's Richard Gasquet, Spaniard Fernando Verdasco, Argentina's Juan Monaco, Viktor Troicki of Serbia and Frenchman Julien Benneteau.