The Dimension Data rider blasted his way around a wind-swept 37km time-trial course to record a time of 47:16. His teammate Keagan Girdleston placed second in 48:48 with USN Purefit's former national road champion Darren Lill third in 49:45.
De Bod, the silver medallist behind Darryl Impey in last month's national elite time-trial championships, now leads the general classification with a combined time of 3:05:11. Girdlestone moved into second on 3:06:43 with Lill third in 3:07:40.
In the women's race, Danish superstar Annika Langvad (Spur-Specialized) rose to the occasion after a recent illness to win the stage in 57:21 ahead of former British road champion Sharon Laws in 57:41 and Lise Olivier (Time Freight) in 58:28.
Langvad leads the overall standings with a total time of 3:41:47 ahead of Laws in 3:41:59 and Olivier, runner-up the last two years, in 3:42:41.
"After SA's where I came second behind Darryl and won the U23 title there was a lot of pressure," said the 19-year-old De Bod, who grew up in Stellenbosch.
"Last night I studied the route and it was definitely a goal of mine to win the time-trial.
"This morning I saw it was going to be a headwind start and I knew it was important not to go out too fast, but I did.
"The last stretch of about seven kilometres, where you turn left into the wind, I felt that I was a bit tired. But I was still going well enough and could keep the power up.
De Bod said he would try and put up a good fight now. "I'm not going to make it easy for anyone to take yellow off my shoulders."
He said he had a good team behind him and although they had lost one rider and another was feeling unwell, he believed they could pull it off.
"Tomorrow is going to be a hard stage to focus. My teammates will have to support me until the last climb and hopefully I can take it from there."
Langvad said she knew that she was going well because she wanted to be in good shape for the Cape Epic.
"That being said, I had quite a rough time recently with my health. I've been on antibiotics until Sunday and luckily got the green light to race here.
"I didn't feel 100% yesterday but I hope that I will feel better each day.
She said her strategy was to take the time-trial, presented by Buffet Olives, by feel.
"Even though I had a power meter on my bike, I didn't look at the numbers. I only went by feeling because I know that is how I work the best.
"I think I got the best out of myself today. Of course I got very tired at the end, but I think that is exactly how it has to be."
Langvad said she felt she was in good enough shape to win the tour.
"I feel the upcoming stages suit me. I'm actually very positive."
Results and GC:
Elite men - stage 2 results
1. Stefan de Bod 47:16
2. Keagan Girdlestone 48:48
3. Darren Lill 49:45
Elite men - overall results after stage 2
1. Stefan de Bod 3:05:11
2. Keagan Girdlestone 3:06:43
3. Darren Lill 3:07:40
Elite woman - stage 2 results
1. Annika Langvad 57:21
2. Sharon Laws 57:41
3. Lise Olivier 58:28
Elite woman - overall after stage 2
1. Annika Langvad 3:41:47
2. Sharon Laws 3:41:59
3. Lise Olivier 3:42:41