Newcastle ended a run of five Premier League games without a win thanks to a late goal from Allan Saint-Maximin at St Mary's.
Southampton were reduced to ten men in the first half after Moussa Djenepo was sent off for a high tackle on Isaac Hayden. Referee Graham Scott made the decision after reviewing the challenge on the pitch-side monitor.
The Magpies could have taken the lead in the first half after Sofiane Boufal handled in the area but Matt Ritchie was denied by Alex McCarthy from the penalty spot.
Steve Bruce's side finally took the lead with ten minutes to go when Saint-Maximin fired a shot into the bottom right-hand corner to the delight of the travelling fans.