The meet offered stark contrast of the two sides, with South Sudan coming into the game with a mountain to climb in the face of an unbeaten Ugandan opposition.
Coach Bobby Williamson's men were already into the quarter finals following earlier wins over Kenya and Ethiopia, and the debutants were yet to taste victory or at the very least, a goal.
But the hosts did not leave anything to spare.
Two first half goals by Brian Umony and a strike each by Robert Ssentongo and Diego Hamis Kiiza in the other half were enough to see the home team through a smooth victory.
For a first-timer in the regional tournament, South Sudan displayed plenty of promising football especially against the far more experienced side, the Cranes. It was not a below-par performance at all, they only lacked the experience, this year's tournament being their first ever.
They probed the hosts early into the game, with Zacharia Nasio attempting a shot yards out, only to see it float agonisingly wide.
New faces dominated the home squad which saw Godfrey Kizito and Manco Kaweesa at the heart of the midfield. And they sure played their part effectively, often feeding the troublesome striking line with swift passes that kept Al-Hilal Omdurman-based keeper Jumma Genaro busier than his Ugandan counterpart the other end.
Kiiza's teasing chip that resulted into Uganda's first - and the game's first - corner kick opened the game into early attempts towards the South Sudan goal.
Notable of such moments was when Joseph Ochaya tactically twisted a couple of legs in his wake, tapped in a low aerial ball into the goal's mouth, but the South Sudan defenders threw in their bodies to see it away from the danger zone.
Good enough Serbian coach Zoaran Djordjevic's inexperienced side stood out in height and were able to bring to their possession most of the aerial balls. Their attacks looked ever dangerous and kept keeper Ali Kimera always on his toes.
Mathew Thomas Jacob, who plays for Al-Malakia, came closest to placing his side on the score sheet first right in front of goal but his spirited swing missed the ball.
Uganda Cranes's strength lay mostly in the midfield and the lethal attacking force of Umony, Kiiza and Ssentongo with vital assists from Said Kyeyune down left and Nicholas Wadada on the right wing.
South Sudan had to do plenty of defending in the opening 20 minutes of play with Uganda's striking force - fed by busy midfielders - ever lurking up front. And Uganda's first could not have come at a better time.
A ball from Uganda's third corner found Umony who made a quick decision with his feet to volley home a magnificent opener and his second of the tournament.
Nothing could have inspired the hosts more for more goals than the Vietnam-based striker's goal. And he was to prove that there was more where that came from.
Close to the break, Kyeyune danced his way past some feet down left into the box, sliced a measured pass to Umony who fired it into the net past a beaten Genaro.
Trailing two goals down, Uganda's neighbours had to go back to the dressing room with plenty of things to iron out, if a first goal or win was to be achieved. Coach Djordjevic needed to adjust his attacking plan.
But hardly had they settled into the second half than Ssentongo's early strike worsened matters for the Serbian coach - not the kind of start he had planned for.
And the entire second part of the game would be largely a Cranes affair. Yanga FC player Hamis Kiiza's 78th minute strike dampened the hopes of the South Sudanese even more and it was a point of no return.
Four goals to nothing was too much to take in for a final result, but the freshmen knew they would march towards the exit door of the tournament having etched their first presence in the region's biggest tournament.
The defeat means South Sudan are out of further contention for the title as fellow Group A members Kenya cruised into the quarter finals after thumping Ethiopia 3-1 earlier in the day.
Kenya finish off the group stage in second place (behind Uganda) with six points from three games, Ethiopia in third with only a win over bottom placed South Sudan.