The Stars and Stripes were off to a flying start as Clint Dempsey scored the fifth-fastest goal in World Cup history, netting after just 32 seconds when he cut inside and struck home following a brilliant run down the left.
Despite going down early on, the Black Stars showed their intent and got themselves back into the game with a number of attacking plays, yet were poor in the final third as a host of crosses into the box failed to reach their hard-working captain Asamoah Gyan.
After coming back after the break still a goal down, Ghana continued to press, yet were reduced to long range efforts as the USA defensive line remained solid.
The introduction of Kevin Prince Boateng just before the hour mark proved an inspiration in the midfield for the African giants as the experienced Schalke forward added a much-needed spark into the Ghanaian attack as they searched for the equaliser.
And their long-awaited leveller finally came on 81 minutes as Andre Ayew steered home a sumptuous Gyan backheel to bring his side back in the game, and mount a possible comeback-from-behind victory.
Yet it was not to be, as substitute John Brooks, who was only on the field for the injured Matt Besler, headed home a Zusi corner to hand the lead back to the Jurgen Klinsmann’s men with just four minutes remaining.
Ghana’s 21 attempts on goal and 59% possession was not enough as they failed to mount a threatening attack in the closing stages, the USA holding on for all three points and exercising revenge on Ghana after their Last 16 defeat in South Africa 2010.
USA join Germany on top of Group G, who next face the Ghanaians on 21 June.