Stafford's 59-yard touchdown pass to receiver Golden Tate with 4:48 remaining in the third quarter was the 119th of his career, breaking the old record of 118 held by Bobby Layne.
Layne set the record while playing for the team from 1950-58.
Stafford later added a five-yard touchdown pass to Theo Riddick in the fourth quarter that cut the Lions' deficit to two points.
Stafford, 26, came into Sunday's game in London with 1,891 passing yards, nine touchdowns and six interceptions while completing 63.1 percent of his passes. The completion percentage is currently the second-best of his career, but the 4,322 yards he's on pace for would be his lowest total over a full season in his career.
Before Sunday's game Stafford already held multiple passing records for the Lions, including most career completions, most completions in a season, most touchdown passes in a season and most career passing yards. The Lions selected him No. 1 in the 2009 NFL draft.
The Lions entered Sunday at 5-2 and tied for first place in the NFC North.
- Ben Estes