Southee, who was the most impressive bowler for New Zealand during their drawn test series in Sri Lanka, suffered the injury while diving in the field during a domestic match.
"Tim Southee has unfortunately been ruled out of the Test series against South Africa," a New Zealand Cricket (NZC) statement quoted physiotherapist Paul Close as saying ahead of Friday's opening Twenty20 game in Durban.
"He landed heavily on his thumb while fielding, with scans indicating the ligament has fully ruptured and retracted.
"After consultation with NZC medical staff and a hand specialist it was decided the best course of action is for him to have surgery."
The right-arm paceman, 24, took eight wickets in the second test in Sri Lanka which New Zealand won to level the two-Test series 1-1.
New Zealand have not yet decided on a replacement for Southee for the tour, where the visitors will play two Tests, three one-day internationals and three Twenty20 matches.
"He will commence rehabilitation immediately following the procedure, with a view to him returning to cricket during the home summer," Close added.
"The procedure is likely to keep him out of the game for 6-8 weeks."