The fifth-round draft pick out of Pittsburgh finished 9 of 11 for 81 yards. Peterman played two series, which ended with Jonathan Williams scoring on a 21-yard run and Stephen Hauschka hitting a 30-yard field goal.
There was additional emphasis on Peterman's performance after starter Tyrod Taylor and veteran backup T.J Yates were sidelined by concussions sustained in a 13-9 loss at Baltimore on Saturday.
Taylor has yet to be cleared for practice, but he was healthy enough to attend the game. Though he didn't take part in warmups, Taylor was spotted on the field alongside running back LeSean McCoy about 90 minutes before kickoff.
Coach Sean McDermott declined to update Taylor's status by saying the quarterback remains in the NFL's concussion protocol. McDermott was encouraged by the progress Peterman has shown, while noting Taylor — when healthy — remains the starter.
"I was proud of the way he handled the offense tonight and the game, and the situations he was in," McDermott said. "It's important that we bring him along and do the right things."
Peterman jumped ahead of Yates in taking over the primary backup spot after Buffalo's preseason opener. He finished the preseason going 43 of 79 for 453 yards and a touchdown.
"I definitely think I have made progress, hopefully. I mean, I don't want to be wasting time out there," Peterman said. "I feel I've come a long way with some timing issues and reads and getting a feel for NFL defenses, but still think I've got more steps to do."
Buffalo (1-3) avoided going winless in the preseason, while Detroit (2-2) closed with two consecutive losses.
Lions second-year quarterback Jake Rudock went 6 of 9 for 41 yards in playing the entire first half.
Rookie Brad Kaaya went 12 of 20 for 182 yards with two touchdowns, an interception and lost fumble. Dontez Ford scored on a 6-yard catch, and bad tackling by the Bills led to Tion Green scoring on a 74-yard catch and run midway through the fourth quarter.
Detroit's injury-depleted defensive front showed holes throughout the game.
Buffalo had a 247-89 edge in yards midway through the third quarter, when Joe Banyard scored on a 1-yard run to put the Bills ahead 20-3. Jordan Johnson also scored on a 2-yard run.
Detroit's patchwork defensive line is missing Jordan Hill (bicep), Kerry Hyder (Achilles tendon) and Ziggy Ansah (ankle). Ansah remains on the physically unable to perform list.
Part of the Lions' focus was on the after-effects of Hurricane Harvey. Safety Glover Quin's family lives in Houston, as does tight end Eric Ebron's pregnant fiance. Earlier in the day, Lions owner Martha Ford donated $1 million toward relief efforts.
"It's been very stressful. It's a lot of water. A lot of uncertainty. A lot of panic," Quin told Detroit's WJBK-TV before the game. "And what the Fords did, I know the people in Houston are suffering without a doubt, but I know they very much appreciate it."
Coach Jim Caldwell credited Ford for her contribution.
"A lot of people on the team, even myself, we have relatives down in that area that have been affected by it," Caldwell said. "To see her donate the money to help and try to do what she can was outstanding."
Lions: Had only one listed starter on the field, outside LB Antwione Williams, who opened the game in the middle position.
Bills: LT Cordy Glenn played briefly in making his preseason debut to test his left foot, which had sidelined him for much of the preseason. RT Jordan Mills and RG John Miller also started, though both haven't yet secured starting jobs. Cornerbacks Kevon Seymour and E.J. Gaines both played in the opening quarter in continuing their competition for a starting job.
Lions: OL Cornelius Lucas left in the second half with an ankle injury.
Bills: OL Michael Ola did not return after hurting his left ankle in the first quarter. DL Jerel Worthy sustained a possible concussion when he banged helmets with teammate Joe Powell tackling Rudock on the final play of the first quarter.
Fresh off signing a five-year, $135 million contract extension, Matthew Stafford did all his on-field work about three hours before kickoff, when he spent time throwing passes.
Lions S Charles Washington on competing to make the roster: "Leave it all on the field, leave no doubt. That's what I walked away feeling, and that's all I can ask of myself: die empty. That's our motto in our DB room."
Lions: Open regular season hosting Arizona on Sept. 10.
Bills: Open regular season hosting New York Jets on Sept. 10.