Hughes played more than 50 times for Southampton in the late 1990s and his appointment would end a run of four non-British managers after Mauricio Pochettino, Ronald Koeman, Puel and Pellegrino.
Assistant manager Carlos Compagnucci and assistant first-team coach Xavier Tamarit have also left the club.More news: Mattis Says Some Taliban Factions Might Be Interested In Peace Talks
Changes are coming at Southampton, as the Premier League side attempts to fend off relegation this season. However the team have struggled in front of goal, and he departs with Southampton one place and one point above the bottom three.
An abject display in a 3-0 defeat to relegation rivals Newcastle United proved the final straw, that result making it just one win in their last 17 Premier League games for Southampton.
The straw that broke the camels back proved to come on Saturday with the heavy3-0 defeat toNewcastle United on Saturday, with it now being unknown who will take charge of the FA Cup quarter-final with Wigan Athletic ahead of the global break.More news: '60 Minutes' Snubs the Facts on Education
Under Pellegrino, Southampton have not won a home Premier League fixture since November and their only victory since then came in the form of a 3-2 triumph at fellow strugglers West Brom.
"The club will look to appoint a new management team as soon as possible, with the search for a replacement already under way", a Southampton statement read. The south-coast club chose to act two days after a 3-0 loss at Newcastle, after which Pellegrino said some of his players "gave up".
Pellegrino's sacking has been something that has seemingly been in the pipeline for a matter of months, with Southampton fans having expressed their displeasure with the Argentine for most of the season.More news: Japan's Finance Ministry Doctored Papers In Abe Scandal
'I think Pellegrino has had a good opportunity to turn things around.