The veteran Olympian flashed across the pool in a time of 22.04 seconds to ease into the semi-finals, followed by Brad Tandy (22.42) and Clayton Jimmy (23.12).
Schoeman’s time was also comfortably inside the 22.33 Commonwealth Games qualifying time, meaning he will be allowed to swim the race at Glasgow 2014 if no one else matches the time during the next two rounds.
The six-day competition at the Kings Park Aquatics Centre is doubling as the official qualification event for the July 23 to August 3 spectacle in Scotland and all swimmers must record the stipulated qualifying times if they want to make the Team South Africa squad.
It was also the only morning of the week so far when a qualifying time has come in the heats.
In other heats, Myles Brown was the quickest qualifier in the 1500m freestyle after posting a time of 15 minutes, 24.24 seconds (15:24.24). He was followed by Troyden Prinsloo (15:56.91) and Danie Marais (16:04.34).
Golden boy Chad le Clos, who has already won five titles this week, was quickest in the 200m individual medley, setting a time of 2:06.36.
He finished just ahead of Michael Meyer (2:06.41) and Dylan Bosch (2:06.48).
Among the women, Karin Prinsloo again coasted through the heats as she finished tops in the 200m backstroke and second in the 400m freestyle.
The 24-year-old, winner of three gold medals already in Durban, recorded a time of 2:16.01 in the 200m backstroke. She was followed by Nathania van Niekerk (2:16.71) and Samantha Randle (2:18.11). Prinsloo finished behind Rene Warnes (4:18.20) in the 400m freestyle in a time of 4:21.16. Kyna Pereira (4:24.27) was third.