Foes in the old NFC West from 1970-2001, the Saints and the 49ers have an extensive regular season history. While San Francisco leads the series 46-24-2, New Orleans has captured six of the last seven regular season meetings. The first meeting between the two clubs was a 27-13 Saints loss on October 22, 1967, New Orleans' inaugural season, in San Francisco's Kezar Stadium.
In the 72 regular season games of the series there has been:
• Two seven-game San Francisco winning streaks from 1974-77 and from 1996-99.
• A current six-game regular season winning streak for New Orleans from 2002-10
• A 13-24 record for the Saints in games played in New Orleans, but 4-1 in the last five meetings at the Mercedes-Benz Superdome.
• 34 games decided by double-digits.
• 12 games decided by 21 or more points.
• 35 games decided by a touchdown or less.
| Date | Score | Site | Attendance |
| 10/22/67 | L, 13-27 | Kezar Stadium | 34,285 |
| 11/23/69 | W, 43-38 | Tulane Stadium | 71,448 |
| 10/18/70 | T, 20-20 | Kezar Stadium | 39,446 |
| 12/13/70 | L, 27-38 | Tulane Stadium | 61,940 |
| 9/26/71 | L, 20-38 | Tulane Stadium | 81,595 |
| 11/14/71 | W, 26-20 | Candlestick Park | 45,138 |
| 10/1/72 | L, 2-37 | Tulane Stadium | 69,840 |
| 10/22/72 | T, 20-20 | Candlestick Park | 59,167 |
| 10/21/73 | L, 0-40 | Candlestick Park | 52,881 |
| 12/9/73 | W, 16-10 | Tulane Stadium | 62,490 |
| 9/15/74 | L, 13-17 | Tulane Stadium | 65,071 |
| 12/15/74 | L, 21-35 | Candlestick Park | 40,418 |
| 10/19/75 | L, 21-35 | Candlestick Park | 39,990 |
| 11/23/75 | L, 6-16 | Louisiana Superdome | 40,328 |
| 10/17/76 | L, 3-33 | Candlestick Park | 43,160 |
| 12/12/76 | L, 7-27 | Louisiana Superdome | 42,536 |
| 11/13/77 | L, 7-10 OT | Louisiana Superdome | 41,564 |
| 11/27/77 | L, 17-20 | Candlestick Park | 33,702 |
| 10/15/78 | W, 14-7 | Candlestick Park | 37,671 |
| 12/3/78 | W, 24-13 | Louisiana Superdome | 50,068 |
| 9/23/79 | W, 30-21 | Candlestick Park | 39,727 |
| 11/11/79 | W, 31-20 | Louisiana Superdome | 65,551 |
| 9/7/80 | L, 23-26 | Louisiana Superdome | 58,621 |
| 12/7/80 | L, 35-38 OT | Candlestick Park | 37,949 |
| 9/27/81 | L, 14-21 | Candlestick Park | 44,433 |
| 12/20/81 | L, 17-21 | Louisiana Superdome | 43,639 |
| 11/28/82 | W, 23-20 | Candlestick Park | 51,611 |
| 10/16/83 | L, 13-32 | Louisiana Superdome | 68,154 |
| 11/13/83 | L, 0-27 | Candlestick Park | 40,022 |
| 9/16/84 | L, 20-30 | Candlestick Park | 57,611 |
| 11/25/84 | L, 3-35 | Louisiana Superdome | 65,117 |
| 9/29/85 | W, 20-17 | Candlestick Park | 58,053 |
| 12/15/85 | L, 19-31 | Louisiana Superdome | 46,065 |
| 9/21/86 | L, 17-26 | Candlestick Park | 58,297 |
| 11/2/86 | W. 23-10 | Louisiana Superdome | 53,234 |
| 10/25/87 | L, 22-24 | Louisiana Superdome | 60,497 |
| 11/15/87 | W, 26-24 | Candlestick Park | 60,436 |
| 9/4/88 | L, 33-34 | Louisiana Superdome | 66,357 |
| 12/11/88 | L, 17-30 | Candlestick Park | 62,977 |
| 10/8/89 | L, 20-24 | Louisiana Superdome | 60,488 |
| 11/6/89 | L, 13-31 | Candlestick Park | 60,667 |
| 9/10/90 | L, 12-13 | Louisiana Superdome | 68,629 |
| 12/23/90 | W, 13-10 | Candlestick Park | 60,112 |
| 11/10/91 | W, 10-3 | Louisiana Superdome | 68,591 |
| 12/1/91 | L, 24-38 | Candlestick Park | 62,092 |
| 9/27/92 | L, 10-16 | Louisiana Superdome | 68,591 |
| 11/15/92 | L, 20-21 | Candlestick Park | 64,895 |
| 9/26/93 | W, 16-13 | Louisiana Superdome | 69,041 |
| 11/22/93 | L, 7-42 | Candlestick Park | 66,500 |
| 9/25/94 | L, 13-24 | Candlestick Park | 63,971 |
| 11/28/94 | L, 14-35 | Louisiana Superdome | 61,304 |
| 9/3/95 | L, 22-24 | Louisiana Superdome | 66,627 |
| 10/29/95 | W, 11-7 | 3Com Park | 65,272 |
| 9/1/96 | L, 11-27 | 3Com Park | 63,970 |
| 11/3/96 | L, 17-24 | Louisiana Superdome | 53,297 |
| 9/14/97 | L, 7-33 | 3Com Park | 61,838 |
| 10/26/97 | L, 0-23 | Louisiana Superdome | 60,443 |
| 10/11/98 | L, 0-31 | Louisiana Superdome | 62,811 |
| 11/22/98 | L, 20-31 | 3Com Park | 68,429 |
| 9/19/99 | L, 21-28 | 3Com Park | 67,685 |
| 11/14/99 | W, 24-6 | Louisiana Superdome | 52,198 |
| 11/5/00 | W, 31-15 | Louisiana Superdome | 64,900 |
| 12/10/00 | W, 31-27 | 3Com Park | 67,892 |
| 11/11/01 | L, 27-28 | 3Com Park | 68,083 |
| 1/6/02 | L, 0-38 | Louisiana Superdome | 70,020 |
| 10/20/02 | W, 35-27 | Louisiana Superdome | 67,903 |
| 9/19/04 | W, 30-27 | Louisiana Superdome | 64,900 |
| 12/03/06 | W, 34-10 | Louisiana Superdome | 68,241 |
| 10/28/07 | W, 31-10 | Monster Park | 68,244 |
| 9/28/08 | W, 31-17 | Louisiana Superdome | 70,008 |
| 9/20/10 | W, 25-22 | Candlestick Park | 69,732 |
| 11/25/12 | L, 21-31 | Mercedes-Benz Superdome | 73,147 |
