The Saints are currently 20th in the top flight, with 15 points from 22 games, four from safety after losing 2-1 at home to 10-man Wolverhampton on Saturday.
Jones had only been appointed manager from Luton Town in November on a three-and-a-half-year deal, but has barely lasted three months.
“Southampton Football Club can confirm it has parted company with Men’s First Team Manager Nathan Jones,” the club statement asid.
“First Team Coaches Chris Cohen and Alan Sheehan have also left the club.
“First Team Lead Coach Ruben Selles will take charge of training and prepare the team ahead of next weekend’s game against Chelsea.”
Jones managed only five wins and nine defeats from 14 games in charge, with three of those wins coming in cup competitions.
Southampton had previously dismissed long-time boss Ralph Hasenhuttl after a sluggish start to the campaign, having finished 15th in 2021-22.