The news comes less than 24 hours after the Saints lost 2-1 at home to 10-man Wolverhampton Wanderers on Saturday, consolidating their place at the bottom of the Premier League table.
Jones signed a three-and-a-half-year contract when he replaced Ralph Hasenhuttl in November but lasted just 14 games, losing eight of his nine Premier League games in charge.
Southampton's statement regarding Jones was brief, saying: "Southampton Football Club can confirm it has parted company with Men’s First Team Manager Nathan Jones.
"First Team Coaches Chris Cohen and Alan Sheehan have also left the club.
"First Team Lead Coach Rubén Selles will take charge of training and prepare the team ahead of next weekend’s game against Chelsea."
Jones was named Championship manager of the year last season after guiding Luton Town into the play-offs.
The 49-year-old is the eighth manager in the top flight to be sacked this season after Thomas Tuchel, Steven Gerrard, Bruno Lage, Jesse Marsch, Hasenhuttl, Frank Lampard and Scott Parker.
