He will take charge in October, overseeing their tour of South Africa, followed by a red-ball series in Australia in January and a summer series against India A and Zimbabwe on home soil.
Flintoff, who was seriously injured while filming on the set of BBC's Top Gear show in December 2022, was part of England's white-ball coaching set-up, including the Twenty20 World Cup, where they lost to eventual champions India in the semi-finals.
He recently had a coaching stint with Northern Superchargers in The Hundred.
"It's a fantastic opportunity to work with some of the best up-and-coming talent in the country and to help shape the future of the men's game," Flintoff said in a statement.
"The Lions programme has always been a vital stepping stone for players pushing for international success, and I'm honoured to be part of that journey."
