Bob Bradley's men won all six of their Group G games to cruise into the third round of qualification, but were seeded in Pot 2 for Monday's draw as a result of their poor FIFA Ranking.
And they must now attempt to deny Ghana a third consecutive World Cup finals appearance if they are to avoid a sixth straight qualification failure of their own.
The CAF draw has thrown together a number of other heavyweight clashes, with Ivory Coast's two-legged contest against Senegal among them.
The teams last met in qualifying for the 2013 Africa Cup of Nations, though Senegal were disqualified after the second leg was abandoned due to rioting in the stands in Dakar.
Tunisia are somewhat fortunate to have reached the third round, after they were awarded passage due to Cape Verde's use of an ineligible player during the teams' final group clash.
But Ruud Krol's side will not have it easy against a Cameroon team chasing a seventh World Cup appearance.
Ethiopia were also docked points for the same offence during their campaign, but managed to squeeze through to the next round, where they will face Nigeria.
And in the fifth and final match of the third round of qualifying, Burkina Faso will bid for their first World Cup outing as they take on Algeria.
The first legs of the teams' ties will take place between October 11-15, with the follow-up matches scheduled for November 15-19.
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