Du Plessis ended day one unbeaten on 99 and was made to stew before getting the chance to reach three figures, with a downpour in Port Elizabeth causing play to begin 90 minutes later than planned.
The 30-year-old hit the first ball of the morning, bowled by Jerome Taylor, to the boundary to collect his second Test ton at St George???s Park, having previously achieved that milestone against New Zealand in 2013.
However, Du Plessis was dismissed next up on review, with Snicko proving he had faintly feathered the 229th delivery of his innings through to Windies keeper Denesh Ramdin while looking to play a defensive stroke.
AB de Villiers, playing in his 97th consecutive Test since his debut against England in Port Elizabeth in December 2004, then strode to the wicket to accompany Hashim Amla with the score on 274-3.
But De Villiers and Amla, who put on 308 for the fourth wicket in The Proteas innings and 220 run triumph in the first Test at Centurion last week, were only together for five and bit overs before the heavens opened.
Amla moved from his overnight 17 to 23, while De Villiers thumped Jason Holder for two fours to reach nine, meaning the hosts went into the early lunch break at 289-3 from.
Conditions did not brighten after the interval, though, and the umpires called off the day
South Africa were perched on 270-2 overnight with Du Plessis and Dean Elgar (121) profiting from myriad fielding blips to put on 179 for the second wicket after Alviro Petersen (17) had departed early.
The Proteas, who were sent into bat by West Indies after losing the toss, face the Caribbean outfit in one further Test after this, beginning in Cape Town on January 2, before the sides tangle in three T20Is and five ODIs ahead of the 2015 World Cup in Australia and New Zealand.