The Young Lions fell to a 2-1 loss at the Jakarta International Stadium, with Man City's Joel Ndala's first half goal proving to not be enough to stay in the competition.
Arsenal's Ethan Nwaneri and Myles Lewis-Skelly, Sunderland midfielder Chris Rigg and Chelsea defender Ishe Samuels-Smith were among those making up the Young Lions' side for the clash.
Hashtag United star and Chelsea loanee Ted Curd was on the bench, too, but it wasn't meant to be for the Young Lions.
Ryan Garry's side had finished their group stage campaign with another 2-1 defeat to Brazil, but got through to the knockout stages on goal difference.
England won the competition for the first time in 2017, beating Spain 5-2 with Nottingham Forest's Morgan Gibbs-White and Manchester City's Phil Foden amongst those on the scoresheet.
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Current England first team stars Marc Guehi, Conor Gallagher and Emile Smith Rowe were also in the squad managed by now-Forest boss Steve Cooper.
They then failed to defend their title after being unable to qualify for the last edition of the tournament in 2019.
The 2021 edition of the competition was cancelled due to the Covid-19 pandemic.
Aside from Wednesday's victory, Uzbekistan also impressed when they got themselves out of the group stages in the Under-20s World Cup earlier this year.
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Now, despite being ranked 73rd in the world, their Under-17s have reached their first quarter-final since 2011 where they will either face France or Senegal next.