United's defeat in rain-lashed Huddersfield followed their 0-0 draw at Liverpool last weekend and a laboured 1-0 victory away to Benfica in the Champions League in mid-week
Manchester United fell to a shock 2-1 defeat at promoted Huddersfield Town on Saturday as Pep Guardiola's free-scoring Manchester City moved five points clear at the Premier League summit.
Aaron Mooy and Laurent Depoitre scored at the John Smith's Stadium to give Huddersfield a first win over United since 1952 and condemn Jose Mourinho's side to their first loss of the campaign.
City took full advantage by beating Burnley 3-0, with Sergio Aguero equalling Eric Brook's all-time club scoring record of 177 goals.
Defending champions Chelsea closed to within four points of second-place United by beating Watford 4-2 while Tottenham Hotspur can draw level with Mourinho's men if they beat Liverpool on Sunday.
United's defeat in rain-lashed Huddersfield followed their 0-0 draw at Liverpool last weekend and a laboured 1-0 victory away to Benfica in the Champions League in mid-week.
Things started to go wrong in the 23rd minute when Phil Jones was forced off by an apparent hip injury, with Victor Lindelof taking his place.
Huddersfield went ahead five minutes later when former City player Mooy robbed Juan Mata and followed in to score after David de Gea had saved from Tom Ince.
Lindelof was at fault as Depoitre scored in the 33rd minute, failing to cut out goalkeeper Jonas Lossl's kick, which allowed Depoitre to round De Gea and score.
United substitute Marcus Rashford headed in Romelu Lukaku's cross with 12 minutes remaining, but Huddersfield held firm for a famous win.
Guardiola's City have won their last seven league games, scoring 20 goals in their last four home games.
Argentina striker Aguero netted from the spot on the half hour after Burnley goalkeeper Nick Pope was contentiously adjudged to have fouled Bernardo Silva.
Second-half goals from Nicolas Otamendi and Leroy Sane completed victory.