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The Black Stars put up a listless performance and were duly punished in what was a one-sided first half at the Geodis Park in Nashville, Tennessee.
The USA ran riots in the first half with a double from Giovanni Reyna added to by further strikes from Christian Pulisic and Leon Balogun.
Having lost 2-0 to Mexico last Sunday, Chris Hughton made some changes to his starting line-up for the game against the Yanks.
Abdul Manaf Nurudeen replaced Lawrence Ati Zigi in post, while Alidu Seidu started at right-back. Nicholas Opoku and Jermone Opoku were handed the nod at the centre of defense, while Gideon Mensah maintained his slot at left-back.
In midfield, Thomas Partey started alongside Edmund Addo, with Joseph Paintsil, Jordan Ayew and Mohammed Kudus providing support for centre-forward Inaki Williams.
Gregg Berhalter also named a strong line-up that had the likes of Christian Pulisic, Yunus Musah, Gio Reyna, Tim Weah, Folarin Balogun and Sergino Dest all starting.
After their 3-1 defeat to Germany a few days ago, the USA made a quick start to this game and their early domination paid off when Reyna slammed home from the rebound after just 10 minutes.
The Yanks continued to enjoy unchallenged incursions into Ghana’s area and were awarded a penalty when Pulisic was clumsily brought down in the box.
The AC Milan winger assumed the responsibility himself and scored from the spot to double to home side’s lead in the 22nd minute.
At this point, the USA were cueing up with the chances and Balogon was the next to get on the score sheet when he was given all the time and space to turn in the box and fire the ball home after Gideon Mensah had been dispossessed close to his goal.
Reyna added a fourth late in the first half – easily firing a shot into the net from an indirect free-kick to put the game beyond Ghana’s reach.
The USA took their foot off the gas in the second half and despite a series of substitutions by Hughton to effect the game, neither side could add to the score line as the match ended 4-0.
Meanwhile, the Black Stars have now lost both of the international games they were involved in this month after Mexico also handed them a 2-0 defeat last Sunday.