"To come up and have a breakout game like this is an excellent feeling," Wilson said. "You want to have a good game every game."
Manning threw four touchdown passes to lead the Giants (8-5) as they maintained their NFC East lead.
Manning had TD passes of 6 yards to Martellus Bennett, 5 yards to Domenik Hixon, 25 yards to Hakeem Nicks and 10 yards to Victor Cruz. Wilson scored on runs of 6 and 52 yards and finished with 100 yards on 13 carries on the biggest day of his career.
The loss all but ended the playoff hopes of Drew Brees and the Saints (5-8), who turned the ball over four times in losing their third straight.
49ERS 27, DOLPHINS 13
At San Francisco, Frank Gore ran for a 1-yard touchdown and reached 1,000 yards rushing for the sixth time in his career. Gore finished with 63 yards.
Anthony Dixon also had a 1-yard scoring run and Colin Kaepernick ran for a late 50-yard touchdown and threw for 185 yards in his fourth straight start since being promoted over Alex Smith.
NFL sacks leader Aldon Smith added two to his total for 19½, passing Fred Dean's franchise-best single-season mark of 17½ set in 1983. Smith moved within three sacks of the single-season record Michael Strahan set in 2001 with the New York Giants.
Michael Crabtree had nine catches for 93 yards and rookie LaMichael James ran for 30 yards in a solid NFL debut for the 49ers (9-3-1). Miami is 5-8.
SEAHAWKS 58, CARDINALS 0
At Seattle, Marshawn Lynch had three touchdown runs and Seattle set a franchise record for points. The Seahawks forced eight turnovers. Richard Sherman and Bobby Wagner each had two interceptions.
Seattle (8-5) kept firm grasp on the final NFC wild-card spot and kept alive slim chances of catching San Francisco in the NFC West. The Seahawks also picked up their first division victory and assured coach Pete Carroll of his first eight-win season in three years with the team.
The 58-0 victory was the biggest shutout in Seattle's history.
Arizona (4-9) was shut out for the first time since 2003 against Seattle. The effortless performance will only raise questions about Ken Whisenhunt's future as coach. Arizona lost its ninth straight overall.
"I apologize to our fans and everyone associated with our organization. That was embarrassing," Whisenhunt said.
PACKERS 27, LIONS 20
DaJuan Harris rushed for a score in his first game for the Packers, Aaron Rodgers added the longest TD run of his career, and Mike Daniels returned a fumble 43 yards as the Packers (9-4) opened that one-game lead over Chicago.
The Packers have won 22 straight at home against the Lions, the longest streak in the NFL.
The loss was the fifth straight for Detroit (4-9). Though this wasn't quite as excruciating as the previous three, when the Lions gave up fourth-quarter leads and fell by a total of nine points.
VIKINGS 21, BEARS 14
At Minneapolis, Adrian Peterson rushed for 154 yards and two touchdowns and Harrison Smith returned an interception for a score.
Peterson topped 100 yards before the first quarter was over, helping the Vikings (7-6) remain viable in the NFC wild-card picture.
"The guy's unbelievable. I don't know if he's human or not," Minnesota quarterback Christian Ponder said of Peterson, who wrecked his left knee last December, yet leads the NFL in rushing.
Jay Cutler threw for 260 yards, one touchdown and two interceptions and couldn't finish the game for the Bears (8-5), who have lost four of their last five. He took a wicked hit to the head from Everson Griffen in the fourth quarter and hurt his neck.
COLTS 27, TITANS 23
At Indianapolis, Andrew Luck led the Colts (9-4) back from a 13-point second-half deficit and Adam Vinatieri made two fourth-quarter field goals. Luck has now engineered six fourth-quarter comebacks for Indy, which has a two-game edge in the AFC wild-card race and still can win the AFC South.