| Game Results |
| Teams | Date | Score |
| New Orleans at Atlanta | 9/6/1981 | ATN 35-7 |
| Baltimore at New England | 9/6/1981 | NEA 17-16 |
| New York AFC at Buffalo | 9/6/1981 | NYA 21-14 |
| Seattle at Cincinnati | 9/6/1981 | CIA 38-24 |
| Dallas at Washington | 9/6/1981 | DAN 21-16 |
| Oakland at Denver | 9/6/1981 | DEA 16-10 |
| San Francisco at Detroit | 9/6/1981 | SFN 24-21 |
| Green Bay at Chicago | 9/6/1981 | GBN 38-17 |
| Houston at Los Angeles | 9/6/1981 | LAN 24-14 |
| Kansas City at Pittsburgh | 9/6/1981 | PIA 21-10 |
| Miami at St. Louis | 9/6/1981 | MIA 21-16 |
| Philadelphia at New York NFC | 9/6/1981 | PHN 24-21 |
| Minnesota at Tampa Bay | 9/6/1981 | TBN 24-10 |
| San Diego at Cleveland | 9/7/1981 | SDA 31-0 |
| Pittsburgh at Miami | 9/10/1981 | MIA 35-7 |
| Atlanta at Green Bay | 9/13/1981 | GBN 38-10 |
| Buffalo at Baltimore | 9/13/1981 | BUA 35-21 |
| Cincinnati at New York AFC | 9/13/1981 | CIA 23-16 |
| St. Louis at Dallas | 9/13/1981 | SLN 21-17 |
| Houston at Cleveland | 9/13/1981 | CLA 27-24 |
| Tampa Bay at Kansas City | 9/13/1981 | TBN 17-13 |
| Los Angeles at New Orleans | 9/13/1981 | LAN 30-24 |
| New York NFC at Washington | 9/13/1981 | NYN 26-20 |
| New England at Philadelphia | 9/13/1981 | PHN 24-21 |
| Detroit at San Diego | 9/13/1981 | SDA 23-20 |
| Chicago at San Francisco | 9/13/1981 | SFN 28-3 |
| Denver at Seattle | 9/13/1981 | DEA 38-18 |
| Oakland at Minnesota | 9/14/1981 | OAA 13-12 |
| Philadelphia at Buffalo | 9/17/1981 | PHN 19-7 |
| San Francisco at Atlanta | 9/20/1981 | SFN 28-14 |
| Tampa Bay at Chicago | 9/20/1981 | TBN 35-21 |
| Cleveland at Cincinnati | 9/20/1981 | CLA 16-14 |
| Baltimore at Denver | 9/20/1981 | DEA 21-16 |
| Green Bay at Los Angeles | 9/20/1981 | GBN 19-14 |
| Miami at Houston | 9/20/1981 | HOA 17-9 |
| Detroit at Minnesota | 9/20/1981 | MIN 30-24 |
| New Orleans at New York NFC | 9/20/1981 | NYN 27-7 |
| Seattle at Oakland | 9/20/1981 | SEA 37-21 |
| New York AFC at Pittsburgh | 9/20/1981 | PIA 33-26 |
| San Diego at Kansas City | 9/20/1981 | SDA 28-20 |
| Washington at St. Louis | 9/20/1981 | WAN 40-17 |
| Dallas at New England | 9/21/1981 | DAN 35-21 |
| Buffalo at Cincinnati | 9/27/1981 | CIA 24-10 |
| Atlanta at Cleveland | 9/27/1981 | ATN 30-24 |
| New York NFC at Dallas | 9/27/1981 | DAN 34-0 |
| San Diego at Denver | 9/27/1981 | DEA 17-10 |
| Oakland at Detroit | 9/27/1981 | DEN 27-24 |
| Kansas City at Seattle | 9/27/1981 | KCA 27-21 |
| Miami at Baltimore | 9/27/1981 | MIA 31-17 |
| Minnesota at Green Bay | 9/27/1981 | GBN 27-13 |
| Houston at New York AFC | 9/27/1981 | NYA 21-14 |
| Washington at Philadelphia | 9/27/1981 | PHN 34-23 |
| New England at Pittsburgh | 9/27/1981 | PIA 30-23 |
| New Orleans at San Francisco | 9/27/1981 | SFN 41-17 |
| St. Louis at Tampa Bay | 9/27/1981 | SLN 14-10 |
| Los Angeles at Chicago | 9/28/1981 | CHN 35-21 |
| Baltimore at Buffalo | 10/4/1981 | BUA 17-10 |
| Denver at Oakland | 10/4/1981 | OAA 9-6 |
| Green Bay at New York NFC | 10/4/1981 | GBN 9-0 |
| Cincinnati at Houston | 10/4/1981 | CIA 27-3 |
| Cleveland at Los Angeles | 10/4/1981 | CLA 24-17 |
| Chicago at Minnesota | 10/4/1981 | MIN 20-17 |
| Kansas City at New England | 10/4/1981 | KCA 24-13 |
| New York AFC at Miami | 10/4/1981 | NYA 44-21 |
| Pittsburgh at New Orleans | 10/4/1981 | PIA 43-0 |
| Seattle at San Diego | 10/4/1981 | SDA 27-7 |
| San Francisco at Washington | 10/4/1981 | SFN 45-14 |
| Dallas at St. Louis | 10/4/1981 | DAN 17-7 |
| Detroit at Tampa Bay | 10/4/1981 | TBN 27-20 |
| Atlanta at Philadelphia | 10/5/1981 | PHN 28-0 |
| Cincinnati at Baltimore | 10/11/1981 | CIA 34-17 |
| Detroit at Denver | 10/11/1981 | DEA 34-7 |
| Seattle at Houston | 10/11/1981 | SEA 19-9 |
| Oakland at Kansas City | 10/11/1981 | OAA 27-23 |
| Los Angeles at Atlanta | 10/11/1981 | ATN 31-30 |
| Minnesota at San Diego | 10/11/1981 | SDA 37-20 |
| St. Louis at New York NFC | 10/11/1981 | NYN 14-13 |
| New England at New York AFC | 10/11/1981 | NEA 10-6 |
| Philadelphia at New Orleans | 10/11/1981 | PHN 26-14 |
| Cleveland at Pittsburgh | 10/11/1981 | PIA 34-3 |
| Dallas at San Francisco | 10/11/1981 | DAN 23-3 |
| Tampa Bay at Green Bay | 10/11/1981 | GBN 23-17 |
| Washington at Chicago | 10/11/1981 | WAN 27-13 |
| Miami at Buffalo | 10/12/1981 | BUA 35-24 |
| St. Louis at Atlanta | 10/18/1981 | ATN 23-14 |
| Pittsburgh at Cincinnati | 10/18/1981 | CIA 34-27 |
| New Orleans at Cleveland | 10/18/1981 | CLA 28-24 |
| Los Angeles at Dallas | 10/18/1981 | DAN 21-17 |
| Denver at Kansas City | 10/18/1981 | KCA 24-10 |
| Washington at Miami | 10/18/1981 | MIA 31-14 |
| Philadelphia at Minnesota | 10/18/1981 | PHN 37-7 |
| Houston at New England | 10/18/1981 | HOA 21-17 |
| New York NFC at Seattle | 10/18/1981 | NYN 31-3 |
| Buffalo at New York AFC | 10/18/1981 | NYA 9-6 |
| Tampa Bay at Oakland | 10/18/1981 | TBN 37-31 |
| San Diego at Baltimore | 10/18/1981 | SDA 37-27 |
| San Francisco at Green Bay | 10/18/1981 | SFN 38-10 |
| Chicago at Detroit | 10/19/1981 | DEN 16-7 |
| Denver at Buffalo | 10/25/1981 | BUA 31-21 |
| San Diego at Chicago | 10/25/1981 | CHN 33-31 |
| Baltimore at Cleveland | 10/25/1981 | BAA 41-28 |
| Miami at Dallas | 10/25/1981 | MIA 20-17 |
| Green Bay at Detroit | 10/25/1981 | GBN 17-14 |
| Kansas City at Oakland | 10/25/1981 | KCA 23-9 |
| Cincinnati at New Orleans | 10/25/1981 | CIA 31-17 |
| New York NFC at Atlanta | 10/25/1981 | ATN 28-10 |
| Tampa Bay at Philadelphia | 10/25/1981 | PHN 17-10 |
| Los Angeles at San Francisco | 10/25/1981 | SFN 24-21 |
| Seattle at New York AFC | 10/25/1981 | SEA 26-23 |
| Minnesota at St. Louis | 10/25/1981 | MIN 30-24 |
| New England at Washington | 10/25/1981 | NEA 24-21 |
| Houston at Pittsburgh | 10/26/1981 | HOA 20-13 |
| Atlanta at New Orleans | 11/1/1981 | ATN 34-23 |
| Cleveland at Buffalo | 11/1/1981 | BUA 20-14 |
| Houston at Cincinnati | 11/1/1981 | HOA 31-30 |
| Dallas at Philadelphia | 11/1/1981 | PHN 42-10 |
| Seattle at Green Bay | 11/1/1981 | SEA 20-7 |
| Detroit at Los Angeles | 11/1/1981 | LAN 28-7 |
| Baltimore at Miami | 11/1/1981 | BAA 24-23 |
| New York AFC at New York NFC | 11/1/1981 | NYA 17-14 |
| New England at Oakland | 11/1/1981 | NEA 31-17 |
| Kansas City at San Diego | 11/1/1981 | KCA 43-20 |
| San Francisco at Pittsburgh | 11/1/1981 | PIA 16-13 |
| Chicago at Tampa Bay | 11/1/1981 | CHN 20-13 |
| St. Louis at Washington | 11/1/1981 | WAN 35-31 |
| Minnesota at Denver | 11/2/1981 | DEA 24-17 |
| Chicago at Kansas City | 11/8/1981 | KCA 31-17 |
| Cincinnati at San Diego | 11/8/1981 | CIA 27-23 |
| Cleveland at Denver | 11/8/1981 | DEA 31-21 |
| New York NFC at Green Bay | 11/8/1981 | NYN 24-14 |
| Oakland at Houston | 11/8/1981 | HOA 27-14 |
| Miami at New England | 11/8/1981 | NEA 13-10 |
| Tampa Bay at Minnesota | 11/8/1981 | MIN 22-6 |
| New Orleans at Los Angeles | 11/8/1981 | LAN 17-13 |
| New York AFC at Baltimore | 11/8/1981 | NYA 26-0 |
| Philadelphia at St. Louis | 11/8/1981 | PHN 23-20 |
| Atlanta at San Francisco | 11/8/1981 | ATN 21-19 |
| Pittsburgh at Seattle | 11/8/1981 | PIA 37-13 |
| Detroit at Washington | 11/8/1981 | WAN 37-34 |
| Buffalo at Dallas | 11/9/1981 | DAN 24-7 |
| Los Angeles at Cincinnati | 11/15/1981 | CIA 20-10 |
| Cleveland at San Francisco | 11/15/1981 | SFN 24-0 |
| Denver at Tampa Bay | 11/15/1981 | DEA 31-28 |
| Dallas at Detroit | 11/15/1981 | DAN 19-17 |
| Chicago at Green Bay | 11/15/1981 | GBN 30-13 |
| Houston at Kansas City | 11/15/1981 | KCA 35-27 |
| New Orleans at Minnesota | 11/15/1981 | NON 17-16 |
| New York AFC at New England | 11/15/1981 | NYA 20-3 |
| Oakland at Miami | 11/15/1981 | MIA 20-19 |
| Baltimore at Philadelphia | 11/15/1981 | PHN 35-13 |
| Pittsburgh at Atlanta | 11/15/1981 | ATN 34-21 |
| Buffalo at St. Louis | 11/15/1981 | BUA 23-17 |
| Washington at New York NFC | 11/15/1981 | NYN 23-16 |
| San Diego at Seattle | 11/16/1981 | SEA 42-24 |
| New England at Buffalo | 11/22/1981 | NEA 20-13 |
| Denver at Cincinnati | 11/22/1981 | CIA 30-14 |
| Washington at Dallas | 11/22/1981 | WAN 29-20 |
| Detroit at Chicago | 11/22/1981 | DEN 24-23 |
| Seattle at Kansas City | 11/22/1981 | KCA 41-37 |
| New Orleans at Houston | 11/22/1981 | HOA 27-17 |
| New York NFC at Philadelphia | 11/22/1981 | PHN 21-9 |
| Miami at New York AFC | 11/22/1981 | NYA 30-0 |
| Pittsburgh at Cleveland | 11/22/1981 | CLA 21-9 |
| San Diego at Oakland | 11/22/1981 | SDA 48-0 |
| San Francisco at Los Angeles | 11/22/1981 | SFN 38-14 |
| St. Louis at Baltimore | 11/22/1981 | SLN 23-17 |
| Green Bay at Tampa Bay | 11/22/1981 | TBN 37-6 |
| Minnesota at Atlanta | 11/23/1981 | ATN 17-14 |
| Chicago at Dallas | 11/26/1981 | DAN 30-7 |
| Kansas City at Detroit | 11/26/1981 | KCA 45-10 |
| Atlanta at Houston | 11/29/1981 | ATN 42-27 |
| Washington at Buffalo | 11/29/1981 | BUA 16-13 |
| Cincinnati at Cleveland | 11/29/1981 | CIA 38-24 |
| Green Bay at Minnesota | 11/29/1981 | GBN 31-24 |
| Baltimore at New York AFC | 11/29/1981 | NYA 20-16 |
| Oakland at Seattle | 11/29/1981 | SEA 28-10 |
| Los Angeles at Pittsburgh | 11/29/1981 | PIA 29-14 |
| Denver at San Diego | 11/29/1981 | SDA 21-10 |
| New York NFC at San Francisco | 11/29/1981 | SFN 14-13 |
| St. Louis at New England | 11/29/1981 | NEA 31-28 |
| Tampa Bay at New Orleans | 11/29/1981 | TBN 28-17 |
| Philadelphia at Miami | 11/30/1981 | MIA 17-7 |
| Cleveland at Houston | 12/3/1981 | CLA 37-20 |
| Buffalo at San Diego | 12/6/1981 | SDA 41-10 |
| Minnesota at Chicago | 12/6/1981 | MIN 27-16 |
| Dallas at Baltimore | 12/6/1981 | DAN 45-19 |
| Kansas City at Denver | 12/6/1981 | DEA 27-14 |
| Detroit at Green Bay | 12/6/1981 | DEN 28-9 |
| New England at Miami | 12/6/1981 | MIA 23-20 |
| Los Angeles at New York NFC | 12/6/1981 | LAN 23-9 |
| San Francisco at Cincinnati | 12/6/1981 | SFN 31-14 |
| New York AFC at Seattle | 12/6/1981 | NYA 27-14 |
| New Orleans at St. Louis | 12/6/1981 | NON 34-0 |
| Atlanta at Tampa Bay | 12/6/1981 | TBN 27-20 |
| Philadelphia at Washington | 12/6/1981 | WAN 24-21 |
| Pittsburgh at Oakland | 12/7/1981 | PIA 42-21 |
| Minnesota at Detroit | 12/12/1981 | MIN 24-7 |
| New York AFC at Cleveland | 12/12/1981 | NYA 20-14 |
| Buffalo at New England | 12/13/1981 | NEA 27-20 |
| Chicago at Oakland | 12/13/1981 | CHN 21-17 |
| Cincinnati at Pittsburgh | 12/13/1981 | CIA 35-20 |
| Philadelphia at Dallas | 12/13/1981 | PHN 41-21 |
| Seattle at Denver | 12/13/1981 | SEA 29-24 |
| Green Bay at New Orleans | 12/13/1981 | GBN 24-14 |
| Miami at Kansas City | 12/13/1981 | KCA 37-13 |
| New York NFC at St. Louis | 12/13/1981 | SLN 21-12 |
| San Diego at Tampa Bay | 12/13/1981 | SDA 24-3 |
| Houston at San Francisco | 12/13/1981 | SFN 31-0 |
| Baltimore at Washington | 12/13/1981 | WAN 41-16 |
| Atlanta at Los Angeles | 12/14/1981 | LAN 21-17 |
| Buffalo at Miami | 12/19/1981 | BUA 27-10 |
| Dallas at New York NFC | 12/19/1981 | DAN 27-10 |
| New England at Baltimore | 12/20/1981 | BAA 34-31 |
| Denver at Chicago | 12/20/1981 | DEA 38-14 |
| Cincinnati at Atlanta | 12/20/1981 | CIA 17-10 |
| Pittsburgh at Houston | 12/20/1981 | PIA 24-0 |
| Kansas City at Minnesota | 12/20/1981 | MIN 38-7 |
| Green Bay at New York AFC | 12/20/1981 | GBN 38-34 |
| St. Louis at Philadelphia | 12/20/1981 | PHN 32-10 |
| San Francisco at New Orleans | 12/20/1981 | NON 21-14 |
| Cleveland at Seattle | 12/20/1981 | SEA 29-17 |
| Tampa Bay at Detroit | 12/20/1981 | TBN 29-23 |
| Washington at Los Angeles | 12/20/1981 | LAN 31-7 |
| Oakland at San Diego | 12/21/1981 | SDA 26-23 |