Two tries in three second-half minutes from flanker Pieter-Steph du Toit and wing Kurt-Lee Arendse pulled the Springboks clear and Scotland were unable to find a way back into the contest, barely threatening the South African tryline all game.
Scotland now face a difficult road to qualify from Pool B for the quarter-finals and will likely have to beat Ireland when the teams meet in their final group game in Paris to stand a chance.
Scotland matched South Africa's power in the opening 40 minutes and trailed 6-3 at the break, still in the contest without creating many scoring opportunities.
Once the Boks' powerful forwards came off the bench in the second period, there was another shift in momentum and they were able to comfortably keep the Scots at bay.
That being said, the best chance of the first half fell to the northern hemisphere side as wing Darcy Graham created a three-on-one opportunity but held onto the ball when he needed to release a team mate to canter over the Bok line.
South Africa lost lock Eben Etzebeth after 26 minutes, replaced by RG Snyman, and that changed the dynamic of a scrum battle they had been winning to that point.
Scotland forced a penalty from the set-piece in their own 22, and then shortly afterwards another in range for Russell to secure three points and halve the deficit on the stroke of halftime.
South Africa came out with renewed intensity in the second period, smashing their opponents backwards at the scrum to earn a penalty that put them in Scotland's 22.
From there they moved the ball through phases, gaining a few metres at a time, before Du Toit crashed over from close range.
One try became two three minutes later as Libbok spotted Arendse in acres of space on the right wing and his cross-kick was perfect for the diminutive back to score in the corner.
It was poor defending and a sucker-punch for the Scots, who in truth were out of the contest after 50 minutes and were easily shut-out by the Boks.
Meanwhile, Japan ran in six converted tries as they kicked off their campaign with a 42-12 bonus point win against debutants Chile, who got two tries of their own.
After opening the scoring through a Rodrigo Fernandez early try, the South American team, the lowest ranked at this World Cup, added another from Alfonso Escobar with Santiago Vila slotting over the conversion.
Japan made the most of Chile's two yellow cards to prevail with a brace by Amato Fakatava and other tries from Jone Naikabula, Michael Leitch, Ryoto Nakamura and Warner Dearns, all six being converted by Rikiya Matsuda.
A rousing rendition of the national anthem was followed by a spirited start in the Pool D clash for Chile, the first World Cup debutants since Russia in 2011, and then a dream try in the sixth minute, manufactured with Latin flair and finished off with a dollop of good fortune.
Fullback Inaki Ayarza broke through two tackles to set up the opportunity, but captain Martin Sigren looked to have spoilt it when the ball was knocked out of his hand in the tackle.
It, however, went backwards and quick thinking flyhalf Fernandez pounced on the loose ball, dribbling it forward and then diving on it to dot down. A check by the Television Match Official confirmed the try to the delight of the capacity crowd.
Chilean euphoria lasted less than 120 seconds as they dropped the ball from the kickoff, allowing Japan to score as lock Fakatava showed a fleetness of foot to burst through and sprint away from the defenders for a quick reply.
Basic errors betrayed Chile's naivete and a late tackle from Matias Dittus on fellow prop Koo Ji-won meant a 10-minute spell in the sin bin, during which time Japan went in the lead on the half-hour mark as winger Naikabula stretched over for their second try.
Sigren was also cautioned after head contact in a tackle on Kotaro Matsushima and with the numerical advantage Japan were able to maul over on the stroke of halftime as Fakatava claimed his second try and stretched the lead to 21-7.
But if it was expected the second half would signal the end of the rookies' resistance, the opposite was true as Escobar burst over for a 48th minute try to fire up the crowd and cut Japan's lead to nine points.
That was as good as it got for the gutsy Chileans, with Leitch scoring Japan's fourth try in the 53rd minute, centre Nakamura the next 10 minutes from time and 21-year-old Dearns used all of his 2-metre frame to stretch over and score at the end of the game.
"We struggled a little bit against the Chileans' physicality but we executed our gameplan which was great for us," said Japan coach Jamie Joseph.