South Africa was 66-2 before a 113-run partnership between Hashim Amla and Quinton de Kock.
Then, Stuart Broad (3-47) and Ben Stokes (2-77) combined to take four wickets early in the final session for England but South Africa, at 235-6, came back again with an unbroken 74-run stand between bowlers Vernon Philander and Chris Morris.
Returning South Africa captain Faf du Plessis trusted his batting lineup on a cloudy morning at Trent Bridge, choosing to bat in what appeared to be difficult conditions.
England still leads the four-test series after a convincing 211-run win at Lord's in the first game.