Krieg passed for 351 yards and three touchdowns and the Lions' defense harassed Kelly with three sacks and two interceptions in a 35-21 victory Thursday.
The loss left the Bills (6-6) at .500 deeper into the season than at any time since 1987, the last time they failed to qualify for the playoffs.
"This hurts a lot," Kelly said. "Right now, I'm blaming myself because I'm supposed to be the one that can take this team down the field, and I didn't do that."
It is a situation the Bills clearly aren't used to. Usually at this point in the season, the Bills, who have played in the last four Super Bowls, are concerned mainly with wrapping up home-field advantage for the playoffs.
"This team is not going to lay down, despite what happened today," Bill Coach Marv Levy said. "We still have four games to play. Let's play the four games and then talk about it."
The Lions (6-6), who remain alive for a wild-card spot in the NFC playoffs, needed only two plays on two of their four touchdown drives. Kelvin Pritchett, who had only two sacks all season, recorded all three hits on Kelly.
"Defensively, we took a few more chances in this ballgame," Lion Coach Wayne Fontes said. "We sat down and talked about it all week. We couldn't be as passive as we have been. We had to put pressure up front, especially on Kelly, a quarterback who can get a hot hand.
"Our game plan was to really mix it up with the coverages."
For the most part, it worked.
Kelly completed 29 of 35 passes for 273 yards, including a 20-yard touchdown pass to Russell Copeland and a 27-yard scoring pass to Pete Metzelaars.
But the plays that hurt the Bills most were two fourth-quarter interceptions by Detroit safety Willie Clay, one of which he returned 28 yards for a touchdown.
After the first interception, Krieg completed six consecutive passes for 93 yards, including a 12-yard touchdown pass to Brett Perriman that put the Lions ahead, 28-14.
The Bills answered with a 73-yard, eight-play drive with Kelly scrambling in from 15 yards with 4:04 remaining to narrow the gap to seven points again.
On Buffalo's next possession, Clay stepped in front of Thurman Thomas, picked off an underthrown pass and ran untouched for the insurance touchdown.