Andy Carroll's first international goal for England looked to have secured a 1-0 victory for Fabio Capello's side until Sunderland striker Gyan took advantage of hesitant defending to blast home the leveller on 90 minutes.
Gyan's goal was no less than the Black Stars deserved for their contribution to a passionate encounter played out before a crowd of 80,102 fans which included a large and raucous contingent of Ghanaian fans.
England boss Capello fielded a virtual second string side for the game, releasing the Chelsea trio of captain John Terry, Frank Lampard and Ashley Cole along with Wayne Rooney and Michael Dawson.
And despite showing seven changes to the starting XI which defeated Wales 2-0 in a Euro 2012 qualifier last Saturday, England looked to have done enough to secure third straight win until Gyan's late strike.
England took the lead two minutes before the interval through Carroll, making only his second international start following an appearance in a 2-1 defeat by France last November.
Aston Villa's Ashley Young dropped deep and flighted an exquisite ball over the top for club team-mate Stewart Downing.
Downing miscontrolled but the ball fell kindly into the path of the advancing Carroll, who drove hard and low across Ghana goalkeeper Richard Kingson into the bottom corner.
England's lead was no less than the home side deserved after a pulsating period which saw both teams carve out a number of promising openings.
England's defence had any early scare on seven minutes when Kwadwo Asamoah sent Dominic Adiyiah racing clear on goal.
The Partizan Belgrade striker shot low but England goalkeeper Joe Hart spread himself well and managed to block with his legs.
At the other end, England's movement continued to cause problems for Ghana's back four, and both Young and Downing had early chances.
Only a superb one-handed save from Kingson prevented Young from grabbing England's opener on 15 minutes, the Ghana keeper diving at full stretch to turn the Villa playmaker's curling shot behind for a corner.
Young squandered another gilt-edged chance on 24 minutes. Downing picked out James Milner down the right who squared across the six yard box only for Young to some how scoop his close-range shot onto the bar.
That miss might have proved costly for England had it not been for another fine save from Hart.
A free-kick swept in from the right eluded England's defence and Adiyiah dived to head across goal, only to be thwarted by a magnificent one-handed block from the Manchester City goalkeeper.
A lively start to the second half saw Ghana enjoy their best spell of the game, with John Pantsil seeing his shot from the edge of the area deflected just over the bar by Gareth Barry, named as captain in the absence of Terry.
Substitute Jonathan Mensah then headed over a corner from Sulley Muntari as England's defence came under pressure.
England withdrew Carroll to a standing ovation on 59 minutes, the goalscorer being replaced by Tottenham's Jermain Defoe.
With the clock running down England looked to be home only for Gyan to pop up with low shot that beat Hart diving to his right.