Goals on either side of halftime condemned the Americans to defeat, as their defense was exposed badly on both strikes.
The match took place at a near-empty Antonis Papadopoulos Stadium in Larnaca, Cyprus, after a last-minute change of venue from a crisis-hit Ukraine.
It took just 12 minutes before Andriy Yarmolenko put the home team on the board, while Marko Devic doubled the lead midway through the second half against a weak U.S. defense.
The U.S. started with Oguchi Onyewu and John Brooks together at center back – the first time the veteran and the youngster had been paired together. Geoff Cameron slotted into his familiar club role of right back. Sacha Kljestan was given a big chance at center midfield, while the out-of-form duo of Clint Dempsey and Jozy Altidore were played at attacking midfield and forward, respectively.
The USA's backline was torn apart as Ukraine opened up the scoring. Denis Garmash made a run through the U.S. midfield and was played onside by Brooks, who failed to step up in time. In alone on Tim Howard, Garmash saw his shot saved, but on the rebound he set up Yarmolenko for an easy tap-in.
Yarmolenko had a great chance to double his tally when he was played in behind the leaky U.S. defense, but he took his run wide and screwed a right-footed shot wide of the far post. Just minutes later, a poor Kljestan giveaway gave Ukraine another great chance, which it squandered.
The halftime whistle couldn't have come soon enough for the Americans, after an entirely underwhelming display on both sides of the ball in the first half.
The U.S. started the second half well, and Altidore should have done better with his header when Cameron sent in a good cross in the 51st minute.
Though the USA started brightly, it was Ukraine which found the game's second goal and again, the American defense was badly exposed. Substitute Devic was played right through the center of defense. Just like the first goal, Howard made a great initial stop, but the rebound went right back to Devic, who made no mistake with the second opportunity.
Substitute Aron Johannsson nearly scored a great consolation for the U.S. with just minutes to play, but his left-footed volley directly from a corner kick was cleared off the line. It was to be the USA's last good chance on a night it will be keen to forget.