Drew Rosenhaus confirmed to The Associated Press on Saturday night his client had reached a deal with the NFC West champions.
Manningham was expected to depart the New York Giants in free agency after an impressive postseason and fourth quarter performance in the Super Bowl and he will be joining the team he helped beat in the NFC Championship.
Manningham will join an upgraded receiving corps that also includes Randy Moss, who signed a one-year contract Monday, and Michael Crabtree, the team's 10th overall pick in the 2009 draft out of Texas Tech who had 72 receptions for 874 yards and four touchdowns in 2011. San Francisco also remains in the running for free agent quarterback Peyton Manning.
"It's going down. Mario Manningham signs with 49ers. This is a sick WR squad. It's going to be crazy on the Offensive side of the ball," tweeted defensive lineman Ricky Jean Francois.
Manningham finished last season with 39 receptions for 523 yards and four touchdowns in 12 regular-season games. But he caught three touchdowns -- including one against the Niners -- in the postseason and had five receptions for 73 yards against the Patriots, including his sensational 38-yard fourth-quarter catch that set up the game-winning touchdown.
Manningham was a luxury for the Giants, who have Hakeem Nicks and Victor Cruz. Cruz surpassed Manningham last season on the depth chart and general manager Jerry Reese eventually will have to pay both of his top wideouts, leaving Manningham free to go in free agency.
Manningham said during an interview prior to free agency that there were advantages to playing with an elite quarterback such as Eli Manning but that there are other quarterbacks out there.
"He is, but there are a lot of good quarterbacks in this league," Manningham told The Vindicator in Ohio recently. "I just want the ball more, that's all."
And Manningham just wasn't going to see consistent targets with Nicks and Cruz.
The Giants will have to find a new third receiver. Reese and head coach Tom Coughlin said at the NFL Scouting Combine they expect last year's third-round pick, Jerrel Jernigan, to step up this season. Also, the Giants would like to see what the 6-foot-6 Ramses Barden, a 2009 third-round pick, can do as well. They re-signed veteran wide receiver Domenik Hixon, who is coming off a torn ACL injury for the second straight year and still could add another receiver in free agency or the draft.
Manningham, 25, is eager to prove he can be a top receiver. He had a career-high 60 receptions for 944 yards and nine touchdowns in 2010.
"Yeah," he said when asked if he views himself as a top wide receiver and thinks a team will be willing to pay him as such as well. "It's a business. You got to look at it like that too. Their (the Giants) decision might come down to ... you never know. You got to look out for your family. That is how it is."
ESPNNewYork.com's Ohm Youngmisuk and The Associated Press contributed to this report.