Number eight Jasper Wiese, scrum-halves Cobus Reinach and Herschel Jantjies, centre Jesse Kriel, flanker Paul de Villiers, and wingers Jaco Williams and Kurt-Lee Arendse crossed for tries in Durban.
But it was a far from polished performance as the home side also wasted numerous opportunities to make it a much larger win.
Wales were never in the contest and were held scoreless for the second game in a row against the Springboks following a 73-0 home defeat last November, but coach Steve Tandy was pleased with their commitment.
"It was pretty one-sided when it comes to us defending and getting the ball," Tandy said.
"I'm bitterly disappointed with the score but I commend the team around the effort, they stayed in the fight for large parts of the game."
Wales were dealt a blow when replacement prop Ben Warren was given a yellow card and sent to the sin bin after a TMO review picked up his high shot on Marco van Staden.
South Africa handed debuts to four players and rested several regulars, with 20-year-old Vusi Moyo impressing at fly-half as coach Rassie Erasmus continues to grow his player pool.
The 20-year-old Moyo also made his Sharks debut this season and played for the Junior Springboks.
His kickpass to Williams set up a try after the halftime hooter for Kriel and a 19-0 lead that flattered Wales.
