The Dimension Data Continental rider, champion two years ago, headed the elite field with a time of 32:30, provisionally moving into the top spot overall.
Taking second place on the day was his teammate and 2017 champion Kent Main (33:20), followed by ProTouch’s HB Kruger a further 15 seconds adrift.
The 21-year-old De Bod, who lives in Stellenbosch, said at the halfway stage of the 26.5km distance he thought he may have started a bit too fast.
“But, in fact, I was able to keep up my power until the end, so my pacing turned out to be perfect.”
He added that the team’s focus now would be to work hard to protect the yellow jersey.
“The team is working well together and each year things are becoming a bit more professional and the riders are getting more mature,” he said.
“We are a happy outfit and will definitely be aiming for a few more stage victories.”
Spur’s former champion Ariane Luthi finally cracked her first time-trial victory in the race, finishing in 40:25.
Mauritian Aurelie Halbwachs was second, six seconds slower, followed by Demacon’s national road champion Carla Oberholzer in 41:18.
Luthi said she had given it her all and had just managed to handle the pain as she pushed hard all the way to the finish.
“The overall title is my focus so today was very important for that,” she said.
The riders will face a 137km test tomorrow with 2 687m of vertical ascent, ending on top of Du Toitskloof Pass.
Presented by Scicon and the City of Drakenstein, the 491km race ends at the Taal Monument just outside Paarl on Friday.