Manchester City's perfect start to the Premier League season came undone in a shock 2-1 loss to Wolves, but Liverpool missed the chance to go top as they were reduced to nine men in a 2-1 defeat at Tottenham.
Manchester United slumped to another damaging defeat as Crystal Palace won 1-0 at Old Trafford, while Arsenal moved to within one point of the top after cruising to a 4-0 win at Bournemouth.
City had won the opening six games of their title defence as they aim to become the first side to ever claim four consecutive English top-flight titles.
By contrast, Wolves had taken just four points from their first six games, but stunned the champions at Molineux.
Ruben Dias' own goal put the home side in front only for City to respond through Julian Alvarez's free-kick.
Wolves, though, were a constant threat on the counter-attack and got their reward when Hwang Hee-chan swept home at the second attempt 25 minutes from time.
"We have to do more but even when we win we have to do more," said City boss Pep Guardiola, who watched the game from the stands due to suspension.
"When we win and lose we do it together. Today we were not at our best."
City's defeat meant victory would have taken Liverpool top, but Jurgen Klopp's men had a mountain to climb when Curtis Jones was shown a straight red card for going over the top of the ball and making contact with Yves Bissouma after just 26 minutes.
Son Heung-min put Tottenham in front, but the 10 men hit back when Cody Gakpo levelled in first-half stoppage time.
Liverpool were then reduced to nine men as Diogo Jota was shown two quickfire yellow cards.
Yet the visitors held out until the 96th minute when Joel Matip turned Pedro Porro's cross into his own net.
The three points take Tottenham above Liverpool into second, one point behind City, as they remain unbeaten in the Premier League under Ange Postecoglou.
- Man Utd's worst start -
United are now off to their worst ever Premier League start to pile more pressure on Erik ten Hag.
Joachim Andersen's stunning first-half volley separated the sides at Old Trafford.
United had won a League Cup meeting between the sides 3-0 in midweek but with Palace restored to full strength, the Red Devils suffered from a familiar lack of cutting edge up front as they laboured to get back into the game.
"The final part of the game we didn't play our best game," said Ten Hag.
"You have to be sharp and clinical. It's about decision making."
The defeat sees United slip to 10th in the table.
Arsenal moved up to third as Mikel Arteta's men eased to victory at Bournemouth.
Bukayo Saka had been an injury doubt, but was able to make his 87th consecutive Premier League appearance and headed into an empty net to open the scoring.
Saka could have had more had he not then handed over penalty duties to Martin Odegaard and then Kai Havertz before Ben White rounded off the scoring in stoppage time.
- Hat-trick hero Watkins -
Ollie Watkins bagged a hat-trick as Aston Villa thrashed Brighton 6-1.
Two goals from the England striker and a Pervis Estupinan own goal put Villa 3-0 up inside 26 minutes before Ansu Fati reduced the deficit with his first Brighton goal.
But the day belonged to Watkins and he became the first Villa player in 47 years to score two hat-tricks in one season.
Jacob Ramsey and Douglas Luiz piled on the pain for Brighton in the closing stages and did enough to edge Villa ahead of the Seagulls into fifth on goal difference.
Luton secured their first ever Premier League win with a 2-1 victory at Everton.
Tom Lockyer and Carlton Morris were on target for the Hatters, who climb out of the relegation zone.
Sheffield United remain bottom after the Blades were beaten 2-0 at West Ham with Jarrod Bowen and Michail Antonio getting the goals for David Moyes' men.