Manchester United suffered a torrid second-half spell to succumb to defeat against Leicester City in Saturday's headline Premier League clash.
Failure at the King Power Stadium places further questions over Ole Gunnar Solskjaer's tenure ahead of a daunting schedule but neighbours Manchester City did not experience similar problems as the defending champions cruised to yet another victory over Burnley.
City's fellow title contenders Chelsea made London derby history as they battled past Brentford after Liverpool's fearsome front three had comfortably dispatched Claudio Ranieri's new Watford side.
In the other fixtures, Wolves shocked Aston Villa to overturn a two-goal deficit and Norwich City fought for a goalless draw against Brighton and Hove Albion, while Southampton registered their first win over a depleted Leeds United.
Using Opta data, Stats Perform takes a look at the pick of the fixtures from the day.
0 - Norwich remain the only side yet to take the lead in a Premier League match this season. The Canaries haven’t led in any of their last 12 games in the competition, with only Manchester City ever having a longer such run (15 between April and October 1995). Rooted. pic.twitter.com/5wNDrTCqFc— OptaJoe (@OptaJoe) October 16, 2021
Watford 0-5 Liverpool: Mane hits century as Salah continues scoring run
Roberto Firmino became the first Brazilian to score more than one hat-trick in the Premier League as Ranieri fell to defeat by the biggest margin of any manager in their first home game with a new club in the competition.
Firmino's first two goals followed Mane's opener as the Senegal international hit his 100th Premier League goal, without scoring a penalty, with only Les Ferdinand (149) and Emile Heskey (110) previously achieving such a feat.
Mohamed Salah played an exquisite pass for Mane's landmark goal but the Egypt forward also found the net as he danced through Watford's defence to become the joint-top scoring African – level with Didier Drogba (104) – in the history of the competition.
His left-footed curler also made him the first Liverpool player since Daniel Sturridge in 2014 to score in eight consecutive games in all competitions as Jurgen Klopp's side became the first top-flight side to ever score three-plus goals in seven consecutive away games across all competitions.
35y 285d - James Milner is the oldest player to assist a goal for Liverpool in the Premier League since Gary McAllister in October 2001 (36y 299d v Leicester). Timeless. pic.twitter.com/O8ikmoBQfr— OptaJoe (@OptaJoe) October 16, 2021
Leicester City 4-2 Manchester United: Foxes end Red Devils record away run
Mason Greenwood edged United ahead with his fifth strike from outside the box in 21 Premier League goals – only David Beckham and Nani have managed a higher share of goals for the club from in such a fashion of those to score 20 times.
However, just 54 seconds split Marcus Rashford's equaliser for Ole Gunnar Solskjaer's side to make it 2-2 and Jamie Vardy putting the hosts 3-2 to the good.
Patson Daka then became the first Zambian scorer in the Premier League, with 105 different nations now having a goalscorer, as Leicester won three consecutive games in all competitions against the Red Devils for the first time since 1901.
Not only did the Foxes, who have conceded in seven straight top-flight games under Brendan Rodgers, make history they also ended the visitors' record run as 30 games without a loss on the road came to an abrupt end.
1 - This was Manchester United’s first away league defeat in 30 games (since a 2-0 loss at Liverpool in January 2020), and the first time the Red Devils have conceded four goals in an away league game since April 2019 (0-4 vs Everton). Burst. pic.twitter.com/xXmI6T6JOS— OptaJoe (@OptaJoe) October 16, 2021
Brentford 0-1 Chelsea: Blues make history in the capital against unlucky Brentford
Ben Chilwell's third goal in three games – as many as in his last 33 appearances in the league – inspired Chelsea to a record-breaking seventh consecutive away win in London derbies.
Thomas Tuchel's men have conceded just three goals this term – the fewest they have conceded at this stage since 2010-11 (two) – as the Blues won their 15th game against new top-flight opposition in 16 attempts.
Meanwhile, Brentford – who were stifled by Edouard Mendy's 20th clean sheet in 38 games – remain winless in seven matches against Chelsea, losing each of their last three by an aggregate scoreline of 9-0.
20 - Chelsea goalkeeper Édouard Mendy kept his 20th Premier League clean sheet in this game (38th start) – only Petr Cech (26), Pepe Reina (32), Alisson (36) and Roy Carroll (37) have needed fewer starts to reach 20 shut outs in the competition’s history. Saviour. pic.twitter.com/KT14xlFoAG— OptaJoe (@OptaJoe) October 16, 2021
Manchester City 2-0 Burnley: Guardiola's men maintain dominance over the Clarets
City cruised to a comfortable 2-0 victory at Etihad Stadium, meaning they now boast a 32-1 aggregate scoreline over Burnley in their last nine games across all competitions.
Pep Guardiola's side have now kept clean sheets in six of their eight league games this term – more than any other side – as Kevin de Bruyne netted for consecutive top-flight games for the first time since July 2020.
The Clarets, who are on the longest winless run in England's top four tiers (11), are Bernardo Silva's favourite opponent, the Portugal international directly involved in seven goals in eight games.