Manchester United's 100 per cent start to the premier league season came to a dramatic end after a late James Beattie header gave Southampton a 1-0 win in a scrappy match at St Mary's.
The champions had won their first three games but were below their best all day and paid the price two minutes from time when the otherwise excellent goalkeeper Tim Howard failed to collect a corner and left England striker Beattie to head into an empty net.
It was United's first league defeat since December 2002 and hands the early title initiative to rivals Arsenal, the only other team to have won their first three games and who were at Manchester City later on Sunday.
United had struggled to beat Wolverhampton Wanderers 1-0 in midweek and with England midfielder Paul Scholes absent injured on Sunday they again looked jaded and disjointed.
A solid shot by Diego Forlan, parried by Paul Jones, was their best first-half effort while defender Mikael Silvestre failed to make a good contact when given a free header from a corner after an hour.
Kevin Phillips looked sharp for last season's FA Cup runners-up Southampton and Howard did well to block a low shot from the former Sunderland striker in the 67th minute, the American also arching well to touch over a Beattie header in the 74th.
Jones also provided a spectacular save to deflect another swerving Forlan shot six minutes from time as the frustrated champions were reduced to shooting from distance.
The game looked to be heading for a draw, which would have been four in a row for Southampton, until Howard found his way blocked as he came for a Graeme Le Saux corner and Beattie accepted the gift from point-blank range.
"The most important thing was get our first win and remain unbeaten this season," Beattie told Sky Sports TV.
"The lads are very fit and, though the game was a bit slower because of the heat, we felt strong towards the end and had them under pressure."
Southampton manager Gordon Strachan said: "We played well today. I think in the last couple of games we've got back the hunger we had last year.
"The two strikers determined the tempo today, defending from the front and the goal was a reward for all Beattie's hard work."
In Saturday's action Chelsea's two-game 100 percent record ended when they were held to a 2-2 home draw by Blackburn Rovers.
Liverpool collected their first win of the season, Michael Owen scoring twice in a 3-0 success at city rivals Everton, while there were also victories for Leeds United, Fulham, Aston Villa and Birmingham City.