The deal will keep Luke, 23, with the Rabbitohs until the end of the 2015 season.
“I’m really happy about re-signing with the Rabbitohs and to be here for four more years is a dream come true,” Luke said.
“I’ve said before that playing with my brothers every week is what I love, and I regard South Sydney as my home.
“I’d like to thank the Members of the Club and the sponsors for their support and patience as we’ve been working on this contract and I can’t wait to represent you all this season and for the next four years as well.”
Rabbitohs CEO Shane Richardson is pleased to have Issac as part of the Club for the next four seasons.
“Issac is one of the lynchpins in our side, a very important player in terms of the balance of our team, and we’re really happy to have him on board until, at least, 2015.
“He is maturing as a footballer and as a person, and as a young father it was important for him to secure his future with a Club that he knew would look after his best interests.