After the six countries involved in the 'hexagonal round' were unable to agree on the schedule of games, CONCACAF held a draw for the fixtures and the highly anticipated clash between the region's two powerhouses, almost certainly to be held at the Azteca stadium in Mexico City, will be played on March 26.
The US beat Mexico at the Azteca for the first time in a friendly match in August, having failed in the previous 24 attempts.
US coach Juergen Klinsmann, however, said he knew it would be a very different occasion in front of a packed and passionate crowd, expected to be close to 100,000.
"A World Cup qualifier is always different to a friendly game, there is no doubt about that but it was a good feeling to win for the first ever time at Azteca," he said.
"So we go there with all the respect for Mexico, a very good team, but we have a good team as well and we want to go there and get at least one point, if not all three."
The US will host Mexico on September 10 at a venue to be decided in the eighth round of fixtures to determine the three teams that will qualify automatically for the World Cup finals in Brazil in 2014.
Jamaica, Panama, Honduras and Costa Rica are also battling for their ticket to Rio and the fourth placed team in the round-robin qualifying process will face the winner of the Oceania qualifiers in a two-legged playoff for a spot in Brazil.
Mexico, who are the favourites to top qualifying for the North and Central America and Caribbean region, start their campaign at home to Jamaica on Feb. 6 while the US play Honduras away.
"Usually you would like to have your first game at home but if you don't get that you make the best of it and we are looking forward to going to Honduras," said Klinsmann.
"It's an exciting group with very good teams and it will go down right to the last games to decide who is going to the World Cup."