Hamilton-Brown sought a move away from Surrey in the wake of his long-time friend and team-mate Tom Maynard's death in June, and was placed on compassionate leave.
The 25-year-old, who had signed a new deal until the end of 2014 earlier this year, returned to action after a month away but struggled with his form.
Surrey team director Chris Adams announced at the start of September that Hamilton-Brown would be allowed to talk to other counties, and Sussex faced competition from Somerset for his signature.
Hamilton-Brown began his career at Surrey before joining Sussex ahead of the 2008 season. He returned to Surrey for the 2010 campaign, and was made captain at the age of 22 despite his limited first-class experience.
He helped Surrey win the Clydesdale Bank 40 in 2011 and to promotion to Division One of the County Championship.
Now Hove beckons again, with Sussex saying they are "delighted" to have brought in the batsman on a three-year contract.
Hamilton-Brown said: "Losing my best friend Tom in June was indescribably painful. We were extremely close but ultimately I know I will emerge from this awful tragedy with renewed strength and purpose.
"I am delighted to be returning to Sussex, a club where I was previously very happy. I would like to thank Mark Robinson, his coaching staff, the players, management and board at Sussex for welcoming me back so warmly.
"There is nothing like feeling wanted to raise spirits and I fully intend to repay the confidence they have shown in me."
Robinson, Sussex's cricket manager, said of Hamilton-Brown: "He is a very talented cricketer who is yet to reach his full potential, which makes him such an exciting and dangerous player."