The Warwickshire batsman, who has been a regular in the side since making his debut in 2004, has been given a break from Test duty following a disappointing series against Pakistan.
A 16-man party has been selected ahead of the four-match series, which takes place in December and January.
Nottinghamshire opener Alex Hales, who has been tipped to open the batting alongside Alastair Cook, remains in the squad along with his county teammate Samit Patel, who is in as a back-up spinner to Moeen Ali.
Pace bowlers Mark Wood and Steven Finn miss out due to ankle and foot injuries respectively, while all-rounder Adil Rashid has also been left out, with just the one spin bowler likely to be required on South African pitches.
"Playing the number one ranked Test side in the world in their home conditions will be a really exciting challenge for this squad and one I'm sure these players will relish," national selector James Whitaker told the ECB's official website.
"Ian Bell has been an outstanding player for many years and undoubtedly still has plenty to offer England in the future. It was clearly a difficult decision but he has struggled for runs in recent series and we felt that it was the right time for him to take a break and spend time working on his game out of the spotlight.
"The inclusion of Nick Compton and Gary Ballance alongside Alex Hales, Joe Root and James Taylor gives Trevor Bayliss and Alastair Cook plenty of options in the top order."
The first Test begins in Durban on December 26.