| Aug 15 | vs Birmingham City | Bramall Lane, SheffieldParamount+ |
| Aug 22 | @ Swansea City | Swansea.com Stadium, Swansea |
| Aug 29 | @ Cardiff City | Cardiff City Stadium, CardiffCBSSN, Paramount+ |
| Sep 1 | vs Bolton Wanderers | Bramall Lane, Sheffield |
| Sep 5 | vs Norwich City | Bramall Lane, Sheffield |
| Sep 8 | @ Blackburn Rovers | Ewood Park, Blackburn |
| Sep 13 | vs Wolverhampton Wanderers | Bramall Lane, SheffieldParamount+ |
| Sep 19 | @ Stoke City | bet365 Stadium, Stoke-on-Trent |
| Oct 10 | vs Lincoln City | Bramall Lane, SheffieldParamount+ |
| Oct 14 | @ Portsmouth | Fratton Park, PortsmouthParamount+ |
| Oct 17 | @ Bristol City | Ashton Gate, Bristol |
| Oct 24 | vs Derby County | Bramall Lane, Sheffield |
| Oct 30 | vs Wrexham | Bramall Lane, SheffieldParamount+ |
| Nov 3 | @ Preston North End | Deepdale, Preston |
| When | Matchup | Venue and broadcast |
|---|---|---|
| Nov 7 | @ Charlton Athletic | The Valley, LondonParamount+ |
| Nov 21 | vs Watford | Bramall Lane, Sheffield |
| Nov 24 | vs Southampton | Bramall Lane, Sheffield |
| Nov 28 | @ Queens Park Rangers | MATRADE Loftus Road, London |
| Dec 4 | vs West Ham United | Bramall Lane, Sheffield |
| Dec 8 | @ Millwall | The Den, London |
| Dec 12 | vs Burnley | Bramall Lane, Sheffield |
| Dec 18 | @ West Bromwich Albion | The Hawthorns, West Bromwich |
| Dec 26 | vs Middlesbrough | Bramall Lane, Sheffield |
| Dec 29 | @ Derby County | Pride Park, Derby |
| Jan 1 | @ Burnley | Turf Moor, Burnley |
| Jan 16 | vs Bristol City | Bramall Lane, Sheffield |
| Jan 23 | @ Wrexham | STōK Cae Ras, Wrexham |
| Jan 26 | vs Preston North End | Bramall Lane, Sheffield |
| Jan 30 | vs Charlton Athletic | Bramall Lane, Sheffield |
| Feb 6 | @ Watford | Vicarage Road, Watford |
| Feb 13 | @ Wolverhampton Wanderers | Molineux Stadium, Wolverhampton |
| Feb 16 | vs Portsmouth | Bramall Lane, Sheffield |
| Feb 20 | vs Stoke City | Bramall Lane, Sheffield |
| Feb 27 | @ Lincoln City | LNER Stadium, Lincoln |
| Mar 3 | vs Swansea City | Bramall Lane, Sheffield |
| Mar 6 | @ Birmingham City | St. Andrew's Stadium, Birmingham |
| Mar 13 | vs Queens Park Rangers | Bramall Lane, Sheffield |
| Mar 17 | @ West Ham United | London Stadium, London |
| Mar 20 | @ Middlesbrough | Riverside Stadium, Middlesbrough |
| Apr 3 | vs West Bromwich Albion | Bramall Lane, Sheffield |
| Apr 7 | vs Blackburn Rovers | Bramall Lane, Sheffield |
| Apr 10 | @ Norwich City | Carrow Road, Norwich |
| Apr 17 | vs Cardiff City | Bramall Lane, Sheffield |
| Apr 20 | @ Bolton Wanderers | Toughsheet Community Stadium, Bolton |
| Apr 24 | vs Millwall | Bramall Lane, Sheffield |
| May 1 | @ Southampton | St. Mary's Stadium, Southampton |