| 12 Sep 21 | r01        | Kansas City ChiefsKansas City C | 33 - 29 | Cleveland BrownsCleveland Bro |
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| 19 Sep 21 | r02        | Cleveland BrownsCleveland Bro | 31 - 21 | Houston TexansHouston Texan |
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| 26 Sep 21 | r03        | Cleveland BrownsCleveland Bro | 26 - 6 | Chicago BearsChicago Bears |
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| 03 Oct 21 | r04        | Minnesota VikingsMinnesota Vik | 7 - 14 | Cleveland BrownsCleveland Bro |
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| 10 Oct 21 | r05        | Los Angeles ChargersLos Angeles C | 47 - 42 | Cleveland BrownsCleveland Bro |
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| 17 Oct 21 | r06        | Cleveland BrownsCleveland Bro | 14 - 37 | Arizona CardinalsArizona Cardi |
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| 22 Oct 21 | r07        | Cleveland BrownsCleveland Bro | 17 - 14 | Denver BroncosDenver Bronco |
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| 31 Oct 21 | r08        | Cleveland BrownsCleveland Bro | 10 - 15 | Pittsburgh SteelersPittsburgh St |
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| 07 Nov 21 | r09        | Cincinnati BengalsCincinnati Be | 16 - 41 | Cleveland BrownsCleveland Bro |
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| 14 Nov 21 | r10        | New England PatriotsNew England P | 45 - 7 | Cleveland BrownsCleveland Bro |
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| 21 Nov 21 | r11        | Cleveland BrownsCleveland Bro | 13 - 10 | Detroit LionsDetroit Lions |
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| 29 Nov 21 | r12        | Baltimore RavensBaltimore Rav | 16 - 10 | Cleveland BrownsCleveland Bro |
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| 12 Dec 21 | r14        | Cleveland BrownsCleveland Bro | 24 - 22 | Baltimore RavensBaltimore Rav |
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| 20 Dec 21 | r15        | Cleveland BrownsCleveland Bro | 14 - 16 | Las Vegas RaidersLas Vegas Rai |
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| 25 Dec 21 | r16        | Green Bay PackersGreen Bay Pac | 24 - 22 | Cleveland BrownsCleveland Bro |
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| 04 Jan 22 | r17        | Pittsburgh SteelersPittsburgh St | 26 - 14 | Cleveland BrownsCleveland Bro |
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| 09 Jan 22 | r18        | Cleveland BrownsCleveland Bro | 21 - 16 | Cincinnati BengalsCincinnati Be |