Partnerships Amla had partnerships of 92 with Smith, 86 with De Villiers and 102 unbroken with Faf du Plessis (69 not out) to anchor South Africa, which won the first test by an innings and looked on course for another strong showing in the second.
Doug Bracewell led the bowlers with 2-70 but New Zealand has to win in Port Elizabeth to avoid a fourth series loss in five and was facing a large first-innings score by the South Africans after Amla continued his sparkling form from last year.
Amla was called into action after just 10 overs of the test when Alviro Petersen fell to a top edge to fine leg off Bracewell after a tricky opening spell from the New Zealand quicks. They made use of some early pace and bounce on the St. George's Park pitch in the first test here in six years.
But Amla, South Africa's outstanding batsman of 2012, wore them down and hit eight fours in his 19th Test century and fifth in his last eight Tests.
That included his triple century in England and 196 in Australia in South Africa's back-to-back series wins on the road last year.
Brief scores South Africa 325/4 (H Amla 106*, F du Plessis 69*, G Smith 54*)