| 03 Sep 78 | r01        | Cleveland BrownsCleveland Bro | 24 - 7 | San Francisco 49ersSan Francisco |
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| 10 Sep 78 | r02        | San Francisco 49ersSan Francisco | 13 - 16 | Chicago BearsChicago Bears |
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| 17 Sep 78 | r03        | Tennessee TitansTennessee Tit | 20 - 19 | San Francisco 49ersSan Francisco |
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| 24 Sep 78 | r04        | New York GiantsNew York Gian | 27 - 10 | San Francisco 49ersSan Francisco |
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| 01 Oct 78 | r05        | San Francisco 49ersSan Francisco | 28 - 12 | Cincinnati BengalsCincinnati Be |
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| 08 Oct 78 | r06        | Los Angeles RamsLos Angeles R | 27 - 10 | San Francisco 49ersSan Francisco |
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| 15 Oct 78 | r07        | San Francisco 49ersSan Francisco | 7 - 14 | New Orleans SaintsNew Orleans S |
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| 22 Oct 78 | r08        | San Francisco 49ersSan Francisco | 17 - 20 | Atlanta FalconsAtlanta Falco |
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| 29 Oct 78 | r09        | Washington CommandersWashington Co | 38 - 20 | San Francisco 49ersSan Francisco |
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| 05 Nov 78 | r10        | Atlanta FalconsAtlanta Falco | 21 - 10 | San Francisco 49ersSan Francisco |
| 12 Nov 78 | r10        | San Francisco 49ersSan Francisco | 10 - 16 | Arizona CardinalsArizona Cardi |
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| 19 Nov 78 | r12        | San Francisco 49ersSan Francisco | 28 - 31 | Los Angeles RamsLos Angeles R |
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| 28 Nov 78 | r13        | San Francisco 49ersSan Francisco | 7 - 24 | Pittsburgh SteelersPittsburgh St |
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| 03 Dec 78 | r14        | New Orleans SaintsNew Orleans S | 24 - 13 | San Francisco 49ersSan Francisco |
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| 10 Dec 78 | r15        | San Francisco 49ersSan Francisco | 6 - 3 | Tampa Bay BuccaneersTampa Bay Buc |
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| 17 Dec 78 | r16        | Detroit LionsDetroit Lions | 33 - 14 | San Francisco 49ersSan Francisco |