Amajita go head to head against La Celeste Olimpica in what promises to be a thrilling encounter in Incheon, Korea Republic (1pm SA time).
South Africa lost the first two matches against Japan and Italy.
Along with the changes, Senong has also made some positional switches.
First choice goalkeeper Mondli Mpoto will get his third consecutive start between the goals while Malebogo Modise retains his spot at left back with Reeve Frosler occupying the right back position.
In central defence, captain Tercious Malepe will have a new partner in Thendo Mukumela who was at right back in the first match but did not play against Italy.
Having started the first two matches playing alongside Wiseman Meyiwa, Thabo Cele will instead partner with Grant Margeman in the heart of midfield.
Teboho Mokoena gets his first start and has been pushed up the midfield to bolster the Amajita attack.
Masilakhe Phohlongo makes his World Cup debut on the left flank, with Sibongakonke Mbatha continuing on the opposite flank.
Luther Singh has been shifted upfront to be the lone striker.
“This team has the ability to display a great brand of football but the players have to believe in themselves. We worked a lot on set pieces and have encouraged the players to continue playing passing football while building up from the back. Our full backs and flanks will have to be accurate against Uruguay because that is where we can hurt them,” said Senong.
Meyiwa and Sandile Mthethwa start on the bench for the first time in the tournament.
SA U20 starting XI:
Mondli Mpoto (GK); Malebogo Modise; Reeve Frosler; Tercious Malepe (C); Thendo Mukumela; Thabo Cele; Grant Margeman; Sibongakonke Mbatha; Masilakhe Phohlongo; Teboho Mokoena; Luther Singh
SA U20 Subs:
Sanele Tshabalala (GK); Khulekani Khubeka (GK); Shane Saralina; Sergio Kammies; Sandile Mthethwa; Wiseman Meyiwa; Sipho Mbule; Kobamelo Kodisang; Liam Jordan; Keletso Makgalwa