Manchester United were stunned by bottom club Sheffield United in a seismic result for both ends of the Premier League table.
Ole Gunnar Solskjaer's side were expected to regain top spot and end Manchester City's stay at the summit after 24 hours, although Chris Wilder's basement boys had other ideas.
Former City youth product Kean Bryan gave the visitors the lead at Old Trafford but normal service looked to have been resumed when former Blade Harry Maguire headed home.
But Oliver Burke had the final word in the 74th minute, giving Sheffield United a 2-1 triumph – only their second win of the Premier League season.
Brighton and Hove Albion and Fulham could not add to their pair of wins after a goalless draw at the Amex Stadium and sit 10 and five points better off than Wilder's men respectively.
It was the same scoreline at Stamford Bridge as Thomas Tuchel's reign got off to an underwhelming start against Wolves, while Everton against Leicester City also ended all square and there was a thrilling win for Burnley over Aston Villa.
Here are the pick of the Opta facts from some results that might look crucial in the final reckoning.
Manchester United 1-2 Sheffield United: Bryan and Burke land title-race body blow
It was a case of familiar frailties returning to haunt United's title bid as Bryan headed home John Fleck's corner.
Since the start of last season, no team has shipped more goals from corners than the 14 let in by Manchester United, Brighton and Chelsea.
Maguire also made the most of slack set-piece marking to net his sixth league goal for the club and his first at home.
But the hosts' defending from open play left a similar amount to be desired as Burke settled matters via a deflection off Axel Tuanzebe.
Bryan and Burke are the first players to net their maiden Premier League goals in the same match against United since Esteban Cambiasso and Jamie Vardy did likewise for Leicester in 2014.
Four defeats in 10 home matches means the Red Devils have amassed their highest number of league losses at Old Trafford since going down in seven in 2013-14.
Sheffield United became the first team from Yorkshire to win a Premier League game at Manchester United and only the third side in the Premier League era, following Leeds United in January 2010 (FA Cup) and York City in September 1996 (League Cup).
Chelsea 0-0 Wolves: Possession without penetration for Tuchel's Blues
A day after being installed as Frank Lampard's successor, Tuchel saw his swiftly remodelled Chelsea dominate but fail to find the net against Wolves.
Struggles against Nuno Espirito Santo's side are nothing new, no matter who is in charge. This is the second time in three seasons that Wolves have gone unbeaten versus Chelsea, having also won at Molineux and drawn at Stamford Bridge in 2018-19.
The visitors certainly had to work to keep their opponents at bay as the Blues hogged 78.9 per cent of possession and racked up 820 passes. Since Opta began collecting this data in 2003-04, both are the highest totals by a team in their coach's first match in charge.
Tuchel is on a run of four consecutive league clean sheets after Paris Saint-Germain completed shutouts in his final three Ligue 1 matches.
Before this season, Thiago Silva was a key part of his backline in the French capital. Reunited in London, the Brazil veteran is now unbeaten in 25 home league appearances under Tuchel (W22 D3).
Wolves have not been so assured defensively of late and this was their first league clean sheet since a 2-0 win over Crystal Palace on October 30, ending a run of 12 straight games without one.
Burnley 3-2 Aston Villa: Wood heads for the heights to lift Clarets
Chris Wood netted a 79th-minute winner as Burnley twice came from behind at Turf Moor to beat Aston Villa and move nine points clear of the relegation zone.
Wood rose to nod home a cross from winger Dwight McNeil for something of a trademark goal. Since his top-flight debut for Burnley in August 2017, no player has scored more headed goals than the New Zealand striker, who is level with Harry Kane on 15.
McNeil pulled Sean Dyche's side level after Jack Grealish netted his sixth league goal of the campaign. Combined with his eight assists, the England star has 14 goal involvements in 18 Premier League matches – the same number he managed last season (eight goals, six assists).
Ollie Watkins matched Grealish's goals mark from 2019-20 when he opened the scoring, making it eight Premier League goals in 18 outings.
Ashley Westwood got the assist for Ben Mee's initial equaliser, meaning he has 16 assists for Burnley in the competition. Only Johann Gudmundsson (17) has more.
Everton 1-1 Leicester City: Long-range lone ranger James shines again
James Rodriguez continued his fine form for Everton with a spectacular strike to put Carlo Ancelotti's men in front.
The Colombia international has scored 19 goals from outside the box in Europe's top five leagues – three for Monaco, 11 for Real Madrid, three for Bayern Munich and now two for Everton.
This was his first with his right foot and added to an impressive personal haul of four goals and three assists. Only Dominic Calvert-Lewin (11) has been directly involved in more Premier League goals for Everton this season.
However, another specialist made sure the points were shared. All five of Youri Tielemans' goals for Leicester in the league this season have come away from home.
The Belgium international has netted the most away goals of any player yet to score at home this term.
Everton might well have a further say in the title battle to come. They are unbeaten in the three league games they have played against opponents starting the day above them in the table this season – a 1-0 win over Chelsea and 2-0 defeat of Leicester last December.
Brighton and Hove Albion 0-0 Fulham: All square in tense basement battle
High stakes did nothing for the entertainment value in this relegation six-pointer, completing a pair of 0-0 draws between Brighton and Fulham this season.
Perhaps it was not for the want of trying – with 26 shots combined (16 for Brighton and 10 for Fulham), only Aston Villa v Burnley (33) last month and Leeds United v Arsenal (34) in November have produced more shots without a goal being scored in 2020-21.
It was the first time Fulham have played out two goalless draws against the same opponent in a single season since a pair of 2001-02 stalemates with Leicester.
Brighton have become bore-draw specialists, playing out 14 0-0s since their promotion to the top-flight in 2017-18, which is more than any other side in that period.
As their positions in 17th and 18th illustrate, both teams are finding victories hard to come by.
Fulham are winless in nine, with six draws and three losses, since beating Leicester 2-1 in November, while Brighton's 2-1 triumph against Arsenal in June is their only win in the past 19 matches at the Amex Stadium. Since then they have lost and drawn seven apiece on home turf.