Leeds began their Premier League campaign against rivals Manchester United at Old Trafford on 14 August 2021, live on BT Sport, losing by a score of 5–1.

After the half-time interval, Luke Ayling levelled the scores, with his first Premier League goal for Leeds.

Mason Greenwood then put Manchester United ahead again in the 52nd minute, after Paul Pogba released him down the left wing.

Fred then scored Manchester United's fifth goal in the 68th minute after a fourth assist from Pogba, a joint-Premier League record for a single match.

[4] Leeds' following match was against League One club Crewe Alexandra at Elland Road in the EFL Cup second round on 24 August, winning 3–0.

[5] Leeds travelled to Turf Moor to play Sean Dyche's Burnley on 29 August, drawing 1–1.

Burnley opened the scoring after a Matthew Lowton shot fell into former Leeds player Chris Wood's path, allowing him to prod the ball home; however, Leeds equalised through Bamford after a Jamie Shackleton shot fell into his path so he could foot it into the Burnley goal past Nick Pope.

[6] Leeds' first match after the first international break of the season saw them host Jürgen Klopp's Liverpool at Elland Road on 12 September, losing 3–0 with Pascal Struijk receiving a red card due to a challenge on Harvey Elliott that resulted in a serious injury.

Patrick Bamford scored his second goal of the season in second half stoppage time to earn a point for Leeds.

Leeds' travelled to the London Stadium to face West Ham United on 16 January, winning 3–2.

Leeds started March by travelling to the King Power Stadium to face Leicester City, losing 1–0.

Leeds' press for the final 10 minutes come to fruition, with Jack Harrison scoring a deflected long-shot in second half stoppage time which secured survival.

[13][14] On 18 June 2021, Leeds announced six pre-season friendly matches, against Guiseley, Blackburn Rovers, Fleetwood Town, Real Betis, Ajax and Villarreal.

Last updated: 22 May 2022Source: Soccerbase In addition, Jack Jenkins and Academy players Kris Moore, Nohan Kenneh and Archie Gray were unused substitutes included in at least one matchday squad.