South Africa were cruising in the first two sessions, but West Indies put up a much improved show after tea, picking up five wickets.
Opener Aiden Markram continued his rich vein of form by falling four points short of what could have been his second successive Hundred Test.
Heinrich Klaasen will resume the unbeaten 17 on Thursday with Keshav Maharaj, who has yet to face a ball.
South Africa won the toss and opted to bat, reaching 247 for two at tea with Dean Elgar out for 42 and Markram scored a smooth 96 in which he hit 17 fours.
He attempted to sweep the impressive West Indies spinner Gudakesh Motie (3-75) but could only send the ball to Jermaine Blackwood, who had run after slipping and juggling his catch but held on.
“We felt the pitch was playing well and picked up speed after lunch. We couldn’t really capitalize but hopefully we can get more points in the morning,” Markram told reporters.
“We want to play a nice offensive brand, but it’s still Test cricket and you have to find the right balance. (My shot to get out) was a bit of a cerebral swoon.”
The visitors were crazy with their line and length for the first 60 overs and paid the price, but tightened up in the evening session from a wicket with pace and rebound.
Home captain Temba Bavuma made 28 after his pair of ducks in the first Test before getting his leg jammed before the wicket offered Jason Holder a shot.
Tony from Zorziplaying in his second Test, compiled a first half century with a neat 85 before Motie found a way through his defenses and was knocked down.
Recalled southpaw Ryan Rickelton played some excellent shots but was caught by wicketkeeper Joshua Da Silva off dressmaker Alzarri Joseph who flashed on a wide ball with his score on 22.
Wiaan Mulder was out for 12, played by Kyle Mayers with a ball from length in the swing, while Simon Harmer edged the latter to Da Silva when he had 1.
South Africa won the first test in Pretoria by 87 runs.
(With Reuters entries)
