Leeds began their Premier League campaign against Liverpool at Anfield on 12 September 2020, live on Sky Sports, losing by a score of 4–3.

[1] Mohamed Salah opened the scoring for Liverpool after just four minutes, converting a penalty conceded by Leeds' new signing Robin Koch.

Jack Harrison equalised for the visitors eight minutes later through a low right-footed shot, only for Virgil van Dijk to restore Liverpool's lead with a header.

[2] Leeds continued their winning ways with a 1–0 away victory against early strugglers and Yorkshire rivals Sheffield United on 27 September, with Bamford heading in from a Harrison cross after 88 minutes to score the only goal of the game.

[3] After going behind to Manchester City at home on 3 October, Leeds equalised in the second half with a 59th-minute reply from Rodrigo – his first goal for the club – to finish the match 1–1.

[14] Following criticism aimed at his side, Leeds' Head Coach Marcelo Bielsa defended his style of play and announced he would not change it.

[16] This was followed by a 5–0 "swashbuckling"[17] win just two days later at The Hawthorns, where Alioski, Harrison, Rodrigo and Raphinha all got on the score sheet, and was one of the results that contributed to the relegation of West Brom that season.

A 3–0 defeat at Tottenham Hotspur, saw Harry Kane scoring the opening goal from the penalty spot before Son Heung-min doubled Spurs' lead shortly before half-time.

[18] Leeds, with a number of players out injured, including Kalvin Phillips, came away from Brighton on 16 January with a 1–0 loss, Neal Maupay tapping in a 17th-minute winner past keeper Kiko Casilla, making his first Premier League start in the absence of Illan Meslier.

Cup 3–0 third-round loss at League Two side Crawley Town, all three goals coming in a 20-minute spell early in the second half.

The team fielded by Bielsa was a full-strength one, although many of the second-half substitutions gave first-team playing appearances to youngsters such as Sam Greenwood, Jack Jenkins and Oliver Casey.

After the Brighton result — a third consecutive defeat — Bielsa assessed the team’s form, in a post-match interview, as follows: “Of course it worries me, these are three games that we could have resolved in a different manner.

[23][24] Leeds fought back from 4–0 down at The Emirates through goals by Hélder Costa and Pascal Struijk but still came away from London at the wrong end of Pierre-Emerick Aubameyang’s hat trick,[25] and against Wolves on 19 February, a freakish own-goal by Illan Meslier (a post rebound that went in off the back of his head) was all that separated the teams at full-time and earned him the dubious honour of being the Premier League’s youngest goalkeeper (20 years and 354 days) to score an own goal.

[32] A pair of points from two home draws against Liverpool (1–1)[33] and Manchester United (0–0)[34] marked the only month that season in which Leeds did not lose a game.