Lancaster has come under fire after England were hammered 33-13 by Australia at Twickenham last weekend to become the first host nation to fail to reach the knockout stages of a World Cup.
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The under-pressure head coach has opted to field a much-changed side at the Etihad Stadium, with Exeter Chiefs duo Henry Slade and Jack Nowell making their World Cup debuts at outside centre and wing respectively.
George Ford starts at fly-half after impressing as a half-time substitute against the Wallabies, with Owen Farrell replacing the injured Brad Barritt at number 12 and Danny Care coming in at scrum-half.
Full-back Alex Goode and loosehead prop Mako Vunipola also start, while James Haskell and Nick Easter get their chance in the back row.
Burgess dropped to the bench for the clash with the Wallabies, but the rugby league convert will play no part in England's final game of the tournament, with one bookmaker reportedly having suspended betting on a return to Super League with Leeds Rhinos.
Lancaster said: "Brad Barritt (arm) and Courtney Lawes (knee) are not available this weekend and Ben Morgan (dead leg) and Ben Youngs (ankle) will not be able to train fully until Thursday.
"This is an opportunity for us to finish the tournament with a strong performance against Uruguay and a chance for the likes of young players such as Jack Nowell and Henry Slade to play in a World Cup.
"We owe it to ourselves and the supporters who have been brilliant throughout. This is an important game for rugby in the north of England and we want to give those people who have been looking forward to this game something to cheer about."
England: Alex Goode, Anthony Watson, Henry Slade, Owen Farrell, Jack Nowell, George Ford, Danny Care, Mako Vunipola, Tom Youngs, Dan Cole, Joe Launchbury, Geoff Parling, James Haskell, Chris Robshaw, Nick Easter.
Reserves: Jamie George, Joe Marler, David Wilson, George Kruis, Tom Wood, Richard Wigglesworth, Jonathan Joseph, Mike Brown