Jack Wilshere was an unused substitute as Luis Suarez's brace left England on the brink of elimination from the World Cup.
The Three Lions began brightly with Wayne Rooney going close from a free-kick before crashing a close-range header off the crossbar.
But six minutes before half-time, Suarez drifted in behind Phil Jagielka to head Edison Cavani's cross past Joe Hart and put the South American side ahead.
Rooney saw another chance go begging midway through the second half when he shot straight at Fernando Muslera but was on hand to tap home England's equaliser with 15 minutes remaining after good work from Glen Johnson down the right.
The momentum appeared to have swung England's way but with five minutes remaining, Suarez was first to anticipate Muslera's long kick upfield and kept his composure to thump a clinical finish beyond Hart.