DETROIT -- Cam Newton and the Carolina Panthers learned a harsh lesson: Against the Detroit Lions, even a big lead isn't all that safe.

Newton threw four interceptions, and Carolina squandered a 17-point advantage in a 49-35 loss to Detroit on Sunday. Matthew Stafford rebounded from a rough start to throw five touchdown passes for the Lions, who outscored the Panthers 35-8 in the second half.

"It was as if we were just trying to hold on," Newton said. "You can't do that to a team like that."

The Panthers (2-8) led 24-7 in the second quarter before Stafford got the Lions going

Newton, the No. 1 pick in this year's draft, fell short against Stafford, the top pick in 2009. Newton was 22 of 38 for 280 yards with a touchdown, but the strong-armed passer out of Auburn set a career high with his four interceptions.

After Detroit (7-3) went ahead 35-27, Carolina tied it with 4:59 left in the game on Newton's 6-yard run and 2-point conversion pass to Steve Smith.

Stafford answered quickly with a 30-yard completion to Calvin Johnson, and his final touchdown pass of the game -- a 7-yarder to Brandon Pettigrew -- put Detroit ahead 42-35 with 2:32 left.

Newton then threw an interception on the Panthers' first play after the kickoff. His tipped pass was picked off by Chris Harris, and Kevin Smith's 19-yard scoring run -- his third touchdown of the day -- sealed the win for Detroit.

"It got tipped and disaster happened," Newton said. "It's the small things that are impacting us in a big way."

Newton also ran for two TDs.

Stafford bounced back from throwing two interceptions in the first quarter and finished 28 of 36 for 335 yards.

Kevin Smith ran for a career-high 140 yards for the Lions.

First Quarter

Car-FG Mare 27, 3:55.

Car-Smith 15 pass from Newton (Mare kick), :35.

Second Quarter

Det-K.Smith 28 pass from Stafford (Hanson kick), 14:04.

Car-Pilares 101 kickoff return (Mare kick), 13:50.

Car-Newton 11 run (Mare kick), 9:32.

Det-T.Young 3 pass from Stafford (Hanson kick), 2:57.

Car-FG Mare 31, :00.

Third Quarter

Det-Burleson 16 pass from Stafford (Hanson kick), 10:28.

Det-Scheffler 17 pass from Stafford (Hanson kick), 5:57.

Fourth Quarter

Det-K.Smith 4 run (Hanson kick), 8:02.

Car-Newton 6 run (Smith pass from Newton), 4:59.

Det-Pettigrew 7 pass from Stafford (Hanson kick), 2:32.

Det-K.Smith 19 run (Hanson kick), 2:00.

INDIVIDUAL STATISTICS

RUSHING-Carolina, D.Williams 10-73, Newton 7-37, Stewart 8-22, Smith 1-5. Detroit, K.Smith 16-140, Morris 7-29, Stafford 4-2, K.Williams 1-0, Logan 1-(minus 2).

PASSING-Carolina, Newton 22-38-4-280. Detroit, Stafford 28-36-2-335.

RECEIVING-Carolina, Stewart 6-87, Smith 5-41, LaFell 3-51, Naanee 3-41, Olsen 3-23, D.Williams 1-32, Brockel 1-5. Detroit, Burleson 7-63, Johnson 5-89, K.Smith 4-61, Pettigrew 4-37, R.Davis 2-27, Scheffler 2-24, T.Young 2-14, Heller 1-12, Morris 1-8.

MISSED FIELD GOALS-None.