The Saints are 15th in English football's top flight, three points above the relegation zone, after coming back from 2-0 down in a 2-2 draw away to European champions Chelsea on Wednesday.
But that was not enough to prevent south coast club Southampton sacking Adkins and replacing the Englishman with 40-year-old Argentinian Pochettino, who will take charge of training ahead of Monday's match at home to Everton.
"This decision has been made with the long-term ambitions of Southampton Football Club in mind," said Saints executive chairman Nicola Cortese.
"Whilst we acknowledge the contribution Nigel has made during the past two years, for the club to progress and achieve our long-term targets a change was needed.
"Mauricio is a well-respected coach of substantial quality who has gained a reputation as an astute tactician and excellent man-manager.
"I have every confidence that he will inspire our talented squad of players to perform at the highest possible level.
"He also shares my belief that the most successful clubs are built by nurturing young players through a development system that provides a clear path to the first team, thereby creating a culture that keeps them at the club for the long term.
"This is an approach he has employed with great success in the past and I look forward to him bringing that experience and expertise to Southampton."
Pochettino, in a statement issued by Southampton, added: "This is the kind of opportunity that any coach would relish.
"Southampton is a club with great heritage, and an even more exciting future. There is a clear vision to take the club to a new era of sustained success in the Premier League, and beyond, which I'm delighted to be part of."
Adkins joined Southampton from Scunthorpe in 2010 and took the Saints, then a third-tier club, into the Premier League with back-to-back promotions.
His exit comes with Southampton, who struggled at the start of the season, in the middle of an encouraging run of results which has seen them lose just twice in their last 12 league matches.