Zimbabwe resumed the day on 51-1 in their follow-on innings and opener Takudzwanashe Kaitano made his way to 40 before the breakthrough was made by spinner Senuran Muthusamy.
Another partnership of 39 was formed by Nick Welch and Sean Williams (11) but the latter saw his stumps castled by Proteas captain Wiaan Mulder to the leave the hosts on 103-3.
Welch then combined his skipper Craig Ervine for a stand of exactly 50 with Welch bringing up his third fifty in his fifth Test match.
It was after the lunch interval that a cluster of wickets fell quickly with fast bowler Corbin Bosch destroyer in chief as he picked 4-38, while fellow seamer Codi Yusuf took 2-38 and Muthusamy had figures of 3-77.
Zimbabwe were eventually 220 all out in their second innings in the second session with Welch scoring 55 and Ervine 49, not a huge improvement after being bowled out for 170 in the first innings replying to the Proteas' total of 626-5 declared.
The game will be remembered for Proteas' stand-in skipper Mulder breaking the South Africa record for the highest individual score in Test cricket with an unbeaten 367.
The all-rounder had Brian Lara's world record of 400 in his sights but decided to declare his team's innings at lunch on the second day out of respect to the West Indies great.
Wiaan Mulder broke the record for the Proteas' highest individual score in Test cricket after notching up an unbeaten 367 against Zimbabwe in Bulawayo before the visitors declared on 626-5.
Wiaan Mulder produced a captaincy debut for the ages on Saturday, scoring a record-breaking unbeaten 264 to put South Africa in a dominant position on Day One of the second Test against Zimbabwe.
Lesego Senokwane and Prenelan Subrayen will both make their Test debuts as the Proteas made three changes for the second and final Test against Zimbabwe that starts in Bulawayo on Sunday.
Corbin Bosch admits he has not yet come to grips with matching the feat of legendary Proteas all-rounder Jacques Kallis in the first Test victory against Zimbabwe in Bulawayo.
