David Kearney moves to full-back while recent call-up Danny Barnes comes into the side at outside centre, replacing Nevin Spence who picked up a wrist injury during the New Zealand game.
Shane Gahan moves up from the replacements bench to join Barnes in a new-look midfield.
Barnes lined out against Spence in the recent AIB League Division Two play-off final, with both players catching the eye.
Jonny Shiels and Ronan O'Mahony slot in on theright and lef wings while Garryowen and Munster duo Andrew Burke and Conor Murray have both been promoted from the replacements to start at out-half and scrum half respectively.
Ballynahinch pair Paddy McAllister and David McGregor will be joined in the front row by Jack O'Connell, who makes his first appearance of the tournament.
Joe Moran and David O'Callaghan come off the bench to start in the second row, with Rhys Ruddock moving to the blindside flank and Brian O'Hara retaining the openside spot.
Team captain Peter O'Mahony returns to the line-up at number 8, having served his one-match suspension for foul play in the 17-9 win over Argentina.
IRELAND UNDER-20 TEAM & REPLACEMENTS (v Uruguay, IRB TOSHIBA Junior World Championship, Saturday, June 13, Mizuho Rugby Ground, kick-off 1pm local time/5am Irish time):
15 - David Kearney (Lansdowne/Leinster)
14 - Jonny Shiels (Queen's University/Ulster)
13 - Danny Barnes (UCC/Munster)
12 - Shane Gahan (Lansdowne/ Leinster)
11 - Ronan O'Mahony (Garryowen/Munster)
10 - Andrew Burke (Garryowen/Munster)
9 - Conor Murray (Garryowen/Munster)
16 - Thomas Sexton (Old Belvedere/Leinster)
17 - Jack McGrath (St. Mary's College/Leinster)
18 - Mark Flanagan (UCD/Leinster)
19 - Dominic Ryan (Lansdowne/Leinster)
20 - Matthew Healy (Lansdowne/Leinster)
21 - Ian McKinley (UCD/Leinster)
22 - Michael Keating (Clontarf/Leinster)