Georges Prost is to end his five-year spell as Saints' 'technical director' for a similar position with Gerard Houllier's Lyon.
Prost takes over as academy director at the club where he spent the bulk of his playing career when he leaves St Mary's this week.
He said: "It's a combination of several things. My wife Betty wanted to go back home and it's my 28th consecutive season as a coach.
"I'm very demanding of myself on the training field and this is the right time for me to go home.
"Lyon is my home club, I started my career there at 15 and left when I was 25 so it will be a great plasure to go back to my home town after 34 years."
Prost has overseen the development of Theo Walcott, Gareth Bale, Nathan Dyer and Leon Best during five years of success on the south coast.
Saints U19s were national champions in 2004, the U18s won their league in 2005 and in the same season reached the final of the FA Youth Cup.
But that was also the year that Prost, 59, was diagnosed with throat cancer.
He added: "I've been thinking differently since I was ill and want less pressure, but I've really enjoyed my time at Southampton.
"We've had some good results and I'll leave with a lot of positive memories.
"Gareth and Theo have become their country's youngest internationals and last week it was Bale who set up Besty to score for the first team.
"I've tried to bring a little French touch to the academy, we've worked as a team and I'll stay in touch - and be back for the play-off final at Wembley!
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