Although the BCX pair were pushed at times, they eventually got away about midway through the stage to take the top spot on the podium after finishing the 54km course to Franschhoek in 2:11:39.
Andrew Hill and Marco Joubert (TIB Insurance-Momsen Valley Light) followed them home in 2:14:52, with Jurgens Uys and Nicol Carstens (Versus Socks) third in 2:16:50.
Although Woolcock, from Stellenbosch, and Kruger, from nearby Paarl, are riding the race for the first time, they said they were familiar with the area.
Not even a slight spill by Woolcock could derail their winning effort as they exerted the pressure from the outset and never relinquished their lead.
"We spoke about it before the start and knew we had to make an effort on the first climb," said Woolcock. "I also know that section very well so our plan was always to try to get away there."
He said the dry conditions made the route tricky at certain sections and they had to keep their concentration throughout the stage.
"When I did lose a bit of concentration I had a slight front wheel drift and ‘bought a small plot', but no major damage was done," said Woolcock.
"The handlebars were slightly skew, but I managed to straighten them a bit on the fly and then, when we got to a tar section, I took time to loosen a bolt and straighten them properly."
After the early climb, Woolcock said Uys and Carstens came back at them, something the third-placed pair repeated after the leaders made a surge on a second ascent.
"They came back at us on the single-track but I know how things turn out because although we were both putting in a big effort, they were riding five per cent harder just to get back to us.
"We were riding tempo and actually saving energy.
"Once we exited Boschendal on the mountain side towards the Rupert's L'Ormirans Wine Farm, they held on for a few kilometres before we broke away again and kept the gap until the end."
Woolcock said Kruger also had a "little play in the dust" but from then on they rode at an even pace and tried to avoid any serious crashes or mechanicals.
"We took the single-track steadily because it is so dry that even though you know the trails it's very unpredictable. You can come around a corner and the trail can crumble underneath you."
Despite their three-minute lead, Woolcock said they would not be thinking too far ahead, particularly given the quality of the opposition.
"We can't relax at any stage and our opponents are the types of riders who will be on our heels to make the best of any slip-up. You can never count anything out in mountain biking."
In the women's race, Swedish Cape Epic champion Jennie Stenerhag and her South African partner Katie Lennard (Cape Brewing Company) took a firm grip on proceedings by finishing the stage in 2:35:00.
This gives them a decisive lead over Jana Kruger and Ilse Viljoen (Companero), who filled second spot in 3:07:51.
Riding the race for the first time, Stenerhag said they broke away early on and built up a sizeable lead.
"It was a very good day and we rode steadily after getting away from the start," she said.
"The stage was a really good challenge, especially the early climb up to Skyfall when you can definitely feel it in your legs.
"After that it was nice and we felt good throughout as we raced our own race."
The mixed category is led by Corne Barnard and Vera Adrian (dormakaba RA), who finished the stage in 2:27:15, followed by Matthew Stamatis and Carmen Buchacher (Home Ice Cream) in 2:31:51.
TransCape men's champion Pieter Seyffert and An-Li Kachelhoffer (Bestmed-Ellsworth-ASG) were third in 2:40:24.
Tomorrow's second stage will cover a distance of 54km from Franschhoek to Wellington.
Caption: Waylon Woolcock and HB Kruger (front), riding for BCX, set the pace on the opening day of the Liberty Winelands Encounter, in partnership with STANLIB, from Stellenbosch to Franschhoek today. Photo: Ewald Sadie