Substitute Charlie Austin scored seven minutes into his Southampton debut to inflict more Old Trafford pain on a lacklustre Manchester United.
Austin rose to head home a corner in the 87th minute to win an otherwise dour game of few chances.
United and their manager Louis van Gaal were booed off by home fans at full-time after producing just one shot on target in 90 minutes.
Southampton have now won at United in the league for the last two seasons.
Credit: BBC sport