Both receivers were game-time decisions but participated in warmups and tested their injuries before being ruled active. Nicks missed last week's game with a hamstring injury but was able to get through this past week without a setback.
Manningham's knee experienced swelling on Saturday morning, but he ran full speed routes before the game.
Both receivers had touchdowns.
The Giants held out rookie cornerback Prince Amukamara for another week. The team's first-round pick, who has yet to make his pro debut after breaking his foot early in camp, is inactive. Running back Ahmad Bradshaw, wide receiver Jerrel Jernigan, fullback Henry Hynoski, offensive lineman Mitch Petrus, offensive lineman James Brewer and defensive tackle Dwayne Hendricks are also inactive.
Center David Baas played against his former team after missing last week's game with a knee injury.
Defensive lineman Ray McDonald returnd for the 49ers after missing his first game since 2008 last Sunday at Washington because of a hamstring injury.
Ohm Youngmisuk covers the Giants for ESPNNewYork.com. Information from The Associated Press was used in this report.