The Americans opened the scoring after just 31 seconds when Clint Dempsey fired an effort in off the post to claim the fastest goal of the tournament so far.
Here, Sports Mole takes an in-depth look at another thrilling match in Brazil.
On target: 3
On target: 4
Was the result fair?
Despite the USA being in the lead for more than 85 of the 90 minutes tonight, a defeat is harsh on the Ghanaians, particularly in the manner it happened. Having made the worst possible start to the match, they recovered well and started to threaten as the first half went on.
After the interval there was only one team in it in an attacking sense as the Americans looked to protect their slender advantage, while Ghana spent most of their time camped in the opposition half. However, the Africans' poor end product let them down time and time again.
If either side deserved to win this match, it was Ghana, but a draw probably would have been the fairest result. USA deserve credit for overcoming injuries and showing character to respond to a late equaliser, but Ghana only have themselves to blame for not winning this one.
They started slowly as they looked to recover from the shock of conceding within 31 seconds, but once they did ease their way back into the game they were more than a match for the United States. They won't have had too many complaints at going in one down at the break, but by the full-time whistle they will feel that they should have got at least a point from this game.
The African side dominated the second half, asking all of the questions in attack without ever managing to unduly worry the American defence. It was their lack of quality in the final third that was the biggest issue for Ghana today, as they didn't have the incisiveness to break down a stubborn backline.
They improved as the match went on and certainly deserved their equaliser when it came. Indeed, from that point until USA's winner, Ghana were the only team who looked likely to go on and grab a second. They were not at the same level as the side that did so well four years ago, and the prospect of being sent home without a point is now very real with Germany and Portugal to come.
No-one in the USA set-up could have dreamed of a better start to their World Cup. Dempsey giving them the lead after 31 seconds was a perfect way for them to kick off proceedings, but they will perhaps be disappointed that they failed to build upon such an impressive opening.
They weren't helped along the way by injuries, with Jozy Altidore and Matt Besler both having to make way due to hamstring strains - the former of which is likely to be out for the rest of the tournament. However, they still failed to trouble what looked at times to be a suspect Ghanaian defence as much as they should have.
Jurgen Klinsmann sent his side out very defensively in the second half, and being on the back foot for so long is usually asking for trouble. They could have no complaints when Ghana finally did find a way through - despite having defended well - but they still managed to dig out the three points. They will certainly need to improve against Germany and Portugal, but overall a positive start for the Americans.
Sports Mole's man of the match
Kyle Beckerman: It appeared as if Dempsey would once again be the hero for USA when he gave them an early lead, but as the game progressed it was Kyle Beckerman in the middle of the park who emerged as the standout performer. Ghana's fine performances four years ago were inspired by their dynamic midfield, but Beckerman didn't allow any of that tonight.
The central midfielder was everywhere, plugging holes defensively before weighing in when his side attacked. He was forced to do a lot more defending in the second half, but he did so with aplomb. A very impressive performance from the Real Salt Lake man.
This one goes to John Boye for his defending for the opening goal. Perhaps still not in full gear having only been playing for 30 seconds, the defender's attempt at stopping Dempsey was nowhere near good enough. The American slipped the ball past him and then followed with ease before firing his effort in off the post.
Jonas Eriksson was fairly anonymous tonight, which is always a good thing for a referee. He kept his cards in his pocket - perhaps for too long in some instances - but overall he dealt with the match well. There was a potential flash point in the first half when Sulley Muntari seemed to react angrily to Jermaine Jones, but the referee applied common sense and simply calmed the situation down.
Ghana: If Ghana are to stand any chance of progressing now, they will need to beat the impressive Germans next Saturday.
USA: USA, meanwhile, will be looking for a fifth consecutive victory when they take on a wounded Portugal on Sunday.