Jose Mourinho and his Manchester United side endured a week to forget as Watford secured a well-deserved 3-1 victory at Vicarage Road.
Coming off the back of defeats against Manchester City and Feyenoord, United were largely disappointing as Mourinho slipped to three successive defeats as a manager for the first time in over a decade.
The in-form Etienne Capoue struck his fourth goal in six games to put the hosts ahead and although Marcus Rashford levelled on 62 minutes with United's first shot on target, Camilo Zuniga came off the bench and scored almost immediately before a late Troy Deeney penalty secured a memorable 3-1 win for the Hornets -- their first victory over United since 1986.
Mourinho blamed "individual and collective mistakes" for the defeat, while Paul Scholes hit out at the "sloppy" manner of United's play.
Tottenham Hotspur continued their unbeaten start to the Premier League season with a 1-0 win against struggling Sunderland at White Hart Lane.
Spurs took the lead shortly before the hour mark, Harry Kane capitalising on a Papy Djilobodji error to smash home from close range after Kyle Walker's cross had been nodded down by Dele Alli.
But Spurs were rocked late on when Kane was forced off on a stretcher with an ankle injury, while Adnan Januzaj received a second yellow for a late challenge on Ben Davies in the final minute.
That victory lifts Mauricio Pochettino's side into third place but leaves Sunderland 19th with just one point from their opening five fixtures.
Stoke's miserable start the season continued as they were beaten 4-1 by Crystal Palace at Selhurst Park.
Headed goals from James Tomkins and Scott Dann in the ninth and 11th minutes put the Eagles on course for the second Premier League win of the campaign, before James McArthur and Andros Townsend struck in the 72nd and 75th minutes.
Marko Arnautovic scored a consolation goal for Mark Hughes' side in the final minute of added time. The Potters remain bottom of the division with just one point from their opening five games following this latest loss.
Charlie Austin proved his point by climbing off the bench to secure Southampton's first Premier League win of the season as they edged out Swansea at St Mary's Stadium.
The striker was back among the substitutes against the Swans despite his two-goal heroics in the Europa League win over Sparta Prague on Thursday night.
But having watched his teammates spurn a host of chances to take the lead, Austin found the net just 10 minutes after coming on to snatch a 1-0 victory and give Saints boss Claude Puel his first three points in the English top-flight.
It was Austin's first Premier League goal since his debut winner against Manchester United in January, and earned Saints a deserved three points from a dominant display.
Swansea, by contrast, were abject and remain without a win since the opening day of the season.