Ghana on paper playing their easiest game before subsequent matches against Portugal and Germany,made their task of qualification more difficult with the defeat.
It was a sweet victory for USA who avenged their two losses to Ghana at the last two World Cup tournaments.
The Ghanaians were still trying to settle in when USA took the lead inside a minute,leaving them chasing the game early on.
Clint Dempsey scored the fastest goal that has been seen so far in the 2014 FIFA World Cup tournament,finding the net in the 32nd minute.
The US captain latched on to the ball,got the better of John Boye and found the inside post as he rifled the ball low and beyond the keeper to open the scores.
Ghana had the better possession,but coach Jurgen Klinsmann's team were well drilled to withstand the onslaught from the Black Stars.
Jordan Ayew failed to make the right connection to Christain Atsu's cutback,with an effort from him going begging just before the interval.
However the introduction of Kevin Prince Boateng and Michael Essien in the second half brought some invention and guile pushing coach Kwesi Appiah's team.
Asamaoh Gyan had a couple of headed chances that looked troubling but they couldn't go beyond Tim Howard into the net.
Just when it looked as though hopes have been lost,Ghana's patience paid off late in the last ten minutes of the game.
A clever back-heel pass from Gyan played in Andre Ayew who with his inside left foot and under immense pressure found the net for the Black Stars to draw level.
By then the momentum was with the Ghanaians who thronged for another goal,Ayew found space on the left wing but the cutback was poor as Michael Essien couldn't get to the ball in time before it was cleared.
Not quite long,USA found themselves back in front late on in the game.
Jonathan Mensah with a reckless challenge gave away a corner kick which the USMNT capitalised on to get the winning goal.
Substitute John Brooks towered and knocked down a free header to score his side's second goal.
And from the time Brooks scored the goal,it was difficult for Ghana to get back into the game,ending up losing their first match of the World Cup.
Ivory Coast are now the only African team to have won their opening game,with the exception of Algeria who are yet to play.