Miami Heat's Bam Adebayo starred for the 16-time champions, registering a team-high 18 points and seven rebounds in their 103-86 triumph at the Pierre Mauroy Stadium.
The USA led from the first quarter and never looked back, with 14 of Adebayo's points coming before half-time as their star-studded bench maintained their advantage.
For South Sudan, Nuni Omot led the way with a game-high 24 points, but with a team boasting 12 NBA All-Stars, four NBA MVPs and six NBA champions, it proved too much for the Bright Stars.
Kevin Durant (14), Anthony Edwards (13), LeBron James (12), Devin Booker (10) and Derrick White all finished in double figures to ensure there was no repeat of their close encounter with their opponents prior to the Games.
South Sudan led the United States by 16 points in their pre-tournament fixture, but narrowly avoided a huge upset in London as they emerged 101-100 victors.
The United States will face winless Puerto Rico in their final group game this Saturday.
Meanwhile, in the other Group C fixture, Nikola Jokic made Olympic history as he helped Serbia ease to their biggest win at the Games following a 107-66 triumph over Puerto Rico.
Jokic finished with 14 points, 15 rebounds, and nine assists, becoming the first player in Olympic history to record at least 10 points, 15 rebounds, and five assists in a single game.
Filip Petrusev also played his part in the victory, with Serbia knowing they must beat South Sudan in their final group game to qualify for the knockout stages.
Nikola Jokic had 21 points as Serbia overturned a 24-point deficit in Tuesday's quarter-final tie.
Adding to his points tally, Jokic also registered 14 rebounds and eight assists. Team-mate Bogdan Bogdanovic was also on form and finished with 17 points, five rebounds, and six assists.
While Australia had led by 24 points after 13 minutes, a stellar third quarter from Serbia saw them rally to lead.
Tokyo 2020 bronze medallists Australia edged the fourth quarter to force the first overtime of the competition at 78-78 but Jokic's Serbia proved too strong in OT.
They will face either the reigning Olympic champions United States or Brazil in the semis.
On the other side of the draw, Germany overcame Giannis Antetokounmpo's Greece 76-63 to reach their first-ever Olympic semi-finals.
The World Cup champions remain unbeaten in the competition despite Antetokounmpo's 22 points.
Franz Wagner’s 20 points helped the Germans overturn a 12-point deficit to line up a semi-final with the winner of France versus Canada.
"I think it speaks to our maturity," Wagner said. "We even talked about it at half-time, not everything's going to go perfect all the time.
"So you kind of recover from that and adjust and react. I thought we did a good job of responding."
Serbia gave up a 13-point lead in the fourth quarter against the United States on Thursday as they narrowly missed out on a place in the final, but they responded strongly to ensure they did not leave Paris empty-handed.
Jokic was dominant in that game, and he provided the spark once more on Saturday as he finished with a triple-double, getting 19 points, 12 rebounds and 11 assists.
Vasilije Micic matched Jokic's tally of 19, while Bogan Bogdanovic, the program's all-time leading scorer, added 16.
After a promising start to the Olympics by Germany, they have trailed off in recent matches, and they struggled to match the early pace set by Serbia as they fell 30-21 behind in the first quarter.
Though they matched Serbia evenly in the second quarter, any hopes of getting their hands on their first Olympic basketball medal soon faded in the third, with the 19-point gap proving too much for them to turn over.
Serbia claimed their first medal in the Olympic event since earning silver in Rio 2016.
Team USA – who have won gold at the last four editions of the Olympics – looked set to miss out on Saturday's final when Serbia entered the fourth quarter with a 13-point lead.
NBA MVP Nikola Jokic had 17 points and 11 assists for Serbia, who led by as many as 17 points at one stage in the first half.
Bogdan Bogdanovic had 20 points for Serbia while Aleksa Avramovic had 15, but Serbia were unable to hold on and avenge their 110-84 loss to the USA in the group stage.
Golden State Warriors star Curry carried the USA's offense for most of the game, though it was LeBron James' driving layup that tied the contest at 84-84 with under four minutes remaining.
The USA struggled defensively for long periods but finally began to put real pressure on Serbia late in the fourth quarter, and a missed 3-pointer from Ognjen Dobric with Serbia 86-84 up proved decisive.
Curry put the USA ahead with a 3-point jumper on a James assist with two minutes and 24 seconds left, then layups from both players stretched their lead as Serbia wilted.
Twice Serbia drew within two points in the final minute, only for two Curry free throws to seal the USA's victory with eight seconds on the clock.
They will face hosts France – led by NBA Rookie of the Year Victor Wembanyama – in Saturday's gold medal match, after Serbia face Germany for bronze.
James added 12 rebounds and 10 assists to his 16 points to finish with a triple-double, while USA team-mate Joel Embiid brought up 19 points.