They improved to 2-3-1 away from St. Louis this season, and 9-36-1 since the start of 2007.
Bradford finished 19 of 39 for 209 yards and an interception. Steven Jackson had 64 yards rushing and scored on a 1-yard plunge, while Gibson made six catches for 100 yards.
It was a loss for which the Bills (5-8) could only blame themselves.
Safety George Wilson twice had chances to intercept Bradford on the final drive, only to drop the ball. Buffalo's defense also allowed the Rams to convert two third-down chances and a fourth-and-1 on which Bradford hit Austin Pettis for 9 yards.
This marked the second time Buffalo has squandered a lead at home in the final minutes, falling 35-34 to Tennessee on Oct. 21.
The Bills' final drive ended with 12 seconds left when Ryan Fitzpatrick fluttered a pass up the right sideline and linebacker Jo-Lonn Dunbar intercepted.
Fitzpatrick went 25 of 33 for 247 yards passing, including a 2-yard touchdown to Lee Smith.
The Bills' offense shared much of the blame after lacking finish in the first half. Buffalo came away with two field goals on three drives inside the Rams 25. That included Fred Jackson losing a fumble at the Rams 14.
The news got even worse for Jackson, who was helped off the field after appearing to hurt his right leg with about 5 minutes left.
Jackson's leg was sandwiched by two Rams as they made a tackle on a 2-yard run near midfield. With a towel over his head, Jackson was then carted off from the sideline, with fans chanting "Freddie! Freddie!"
Credit the Rams' defense, which limited the Bills to 281 yards and forced two turnovers. Rookie tackle Michael Brockers had 1 1/2 of St. Louis' five sacks.
The Rams persevered on a chilly and wet day, with temperatures in the high 30s, and a light drizzle beginning to fall in the second half.
After being limited to 71 yards and four first-downs in the first half, the Rams got on track to open the second half. Bradford directed an 11-play, 70-yard drive capped by Jackson's plunge to put St. Louis ahead 7-6.
The Bills responded immediately with Smith scoring to cap a seven-play, 75-yard drive.
Buffalo, however, failed on the extra point after the snap slipped through the hands of holder Shawn Powell.
The Rams mustered just three first downs and 66 yards on their next three possessions before Bradford began the decisive drive at his 16 with 4:55 left.
St. Louis 15, Buffalo 12
St. Louis 0 0 7 8 15
Buffalo 3 3 6 0 12
Buf • FG Lindell 35, 2:14.
Buf • FG Lindell 40, :07.
StL • Jackson 1 run (Zuerlein kick), 8:37.
Buf • L.Smith 2 pass from Fitzpatrick (pass failed), 3:26.
StL • Gibson 13 pass from Bradford (Givens pass from Bradford), :48.
Attendance • 68,109.
First downs 17 17
Total Net Yards 285 281
Rushes-yards 27-78 20-61
Passing 207 220
Punt Returns 2-23 4-44
Kickoff Returns 4-88 3-79
Interceptions Ret. 1-21 1-23
Comp-Att-Int 19-39-1 25-33-1
Sacked-Yards Lost 1-2 5-27
Punts 8-37.8 7-39.1
Fumbles-Lost 2-0 2-1
Penalties-yards 2-17 2-15
Time of Possession 29:24 30:36
Rushing • St. Louis, Jackson 19-64, Bradford 4-13, D.Richardson 3-4, Givens 1-(minus 3). Buffalo, Spiller 7-37, F.Jackson 9-14, Fitzpatrick 3-5, Graham 1-5.
Passing • St. Louis, Bradford 19-39-1-209. Buffalo, Fitzpatrick 25-33-1-247.
Receiving • St. Louis, Gibson 6-100, Pettis 5-33, Kendricks 3-36, Givens 3-25, Jackson 1-9, Quick 1-6. Buffalo, St.Johnson 6-71, Chandler 5-71, F.Jackson 5-16, Graham 3-33, Jones 3-33, Spiller 1-15, B.Smith 1-6, L.Smith 1-2.
Missed Field Goals • None.