Steven Finn has been called into the squad as cover but Joe Root confirmed that Wood's spot would go to Roland-Jones who has been part of the squad throughout the series. Wood had managed just 1 for 197 in the opening two Tests of the series.
Roland-Jones, 29, made his ODI debut earlier this season, also against South Africa, at Lord's where he made an unbeaten 37 and took 1 for 34.
In the County Championship this season he has taken 22 wickets at 35.63. Last season he took 54 wickets at 28.22 which included a hat-trick to seal the Championship title for Middlesex.
Roland-Jones' call-up means England will have at least debutants with Tom Westley having previously been confirmed as Gary Ballance's replacement. There could be a third, too, with a decision to be made on Thursday morning between Dawid Malan, the Middlesex batsman, and allrounder Liam Dawson after the pitch remained covered during England's training session due to rain.
"I think it's important to look at the surface and decide what's going to be the best side to play South Africa in those conditions," Root said. "So, we'll turn up tomorrow, take a look at the wicket and make a decision."