Wiese, whose move follows the recent high-profile signings by Hampshire of Kyle Abbott and Rilee Rossouw, will join the county in June, which leaves him a window to play in the IPL should he secure another deal having been released by Royal Challengers Bangalore. He previously played for Sussex in 2016 when he took six wickets in four T20 Blast matches - albeit with an economy above 10 an over - made one Royal London Cup appearance and claimed 19 wickets at 24.00 in six Championship outings.
When Cricket South Africa named their T20 squad to face Sri Lanka later on Monday, they confirmed Wiese had been an original selection but was withdrawn after confirming his Kolpak move.
"I would like to thank Cricket South Africa for giving me the opportunity of fulfilling my lifelong dream of representing my country in the sport I love," Wiese said. "I am very excited to be joining Sussex on a long-term deal. I thoroughly enjoyed my stint with the club last year and it made my decision so much easier when offered to return. Sussex is an extremely ambitious club and I look forward to being part of their future."
Wiese made 26 limited-overs appearances for South Africa - he has a career-best of 5 for 23 in T20Is - without ever being seen as a regular. He has played at the IPL and CPL and remains an important part of the Titans' team but, at 31, and with the amount of young talent coming through, an international future was unlikely. He will join batsman Stiaan van Zyl, who signed for Sussex in November, at Hove.
"We are thrilled to have David joining us at Sussex," Mark Davis, the head coach, said. "He is an extremely accomplished all-round cricketer who is effective in all formats and will bring great experience and skill to our group.
"He will add significantly to our white-ball team with his bowling and powerful batting at the death and has already shown his potential last season in the longer format. His experience will be invaluable to our young developing team."
Vernon Philander will also have a spell with the club as an overseas player before South Africa's tour of England.