The Saints will welcome the Bills (7:20 p.m. CDT) on Thanksgiving Day 2021. New Orleans throttled Buffalo 47-10 in Week 10 of the 2017 season. Saints wideout Michael Thomas hauled in nine receptions for 117 yards in the contest.
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| 7 | 3 | 14 | 7 |
| 0 | 0 | 0 | 6 |
The Saints lead the all-time series 7-4, holding a five-game winning streak against the Bills. New Orleans has posted a 3-3 mark in home contests played against Buffalo, winning in three different facilities; Tulane Stadium (1973), San Antonio's Alamodome (2005) and the Mercedes-Benz Superdome (2013). Kamara had the first 100-yard rushing game of his four-year career against the Bills when he carried 12 times for 106 yards with one touchdown in a 47-10 Saints win at Buffalo's New Era Field on November 12, 2017.
Head Coach: Sean McDermott
Quarterback: Josh Allen
Key Position Players: RB Devin Singletary, WR Emmanuel Sanders, WR Stefon Diggs
Head Coach: Sean Payton
Quarterback: Jameis Winston & Taysom Hill
Key Position Players: RB Alvin Kamara, WR Michael Thomas
