They have won just one game in 17 matches and are just one point above the drop-zone and Pellegrino has paid for his poor form with his job.
Additionally, the club revealed that assistants Carlos Compagnucci and Xavier Tamarit have also left the PL side.
"We would like to place on record our thanks to Mauricio, Carlos and Xavier for their efforts during their time with Southampton, and wish them well for the future", the Southamptonstatement added.
Now in their sixth successive season in the Premier League, Southampton haven't finished lower than 14th in any of the previous five, but face a battle for survival with just eight league games remaining.
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The south-coast club made a decision to act two days after losing at Newcastle 3-0, after which Pellegrino said some of his players "gave up". "I observed some players who gave up and we can not show this, to be honest", he told reporters at his post-match press conference.
Since returning to the Premier League in 2012, Southampton have been successful in managing a high turnover of managers and playing staff.
Speaking on BBC Radio 5 live, former Southampton star Francis Benali said: 'It is something that has been bubbling away and has been talked about by Southampton fans for a while.
Pellegrino was appointed at St Mary's Stadium in June as a replacement for the sacked Claude Puel, who had led the club to the CarabaoCup final and an eighth-place finish in his one season in charge, and has since been appointed by Leicester City.
'I think Pellegrino has had a good opportunity to turn things around.
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