The Saints were seeking to replace Adam Asghar, who left at the end of the 2023/24 season.
Now Rusk has come in and will work with the U21s as they get ready for the 2024/2025 season in Premier League 2.
After arriving, Rusk said: "I'm delighted to join Southampton, it's an exciting step to come to a club with such an established reputation for developing top talent.
"I'm looking forward to getting started with the group here, having spoken with Andy our visions are shared in wanting to push the Academy forward again both on and off the pitch."
Academy Director Andy Goldie added: “The appointment of Simon highlights the importance placed of the final stage of the Academy journey for our most exciting young talent.
"After reviewing our performance as an Academy last season, there was a clear profile we required for this role and it was evident that Simon possessed the qualities and experience to help deliver on our objectives.
"His track record in developing young talent at club and International level speaks for itself, but he will also act as a great mentor for our younger coaches and play a key role in driving the Academy forward next season.”