The two teams regularly battle each other in the qualifiers for the World Cup and on Saturday, they will clash in the final of the Gold Cup, the third time in a row they have played each other in the championship decider.
The stakes are high. The winner will earn a place in the 2013 Confederations Cup in Brazil and bragging rights as the region's best team.
Mexico have traditionally been the strongest team, winning 32 of their 58 previous clashes, and are unbeaten at home. The Americans have won 15 and there have been 11 draws.
The teams first played each other in 1934, in a qualifier for the World Cup. The match was played in Italy and the Americans won 4-2, with all four goals from Aldo Donelli, but it was not a sign of things to come.
Spurned by their defeat, Mexico won their next 10 matches against their northern neighbors between 1937 and 1957, racking up 56 goals.
It was not until 1980, in a meaningless World Cup qualifier that had no bearing on the series, that the Americans finally recorded their second win over El Tri, 46 years after the first.
The first U.S win that really counted for something came in the 1991 Gold Cup semi-final in Los Angeles. The Stars and Stripes won the match and went on to win their first major tournament.
Two years later, Mexico re-established their dominance in emphatic fashion with a 4-0 victory in the Gold Cup final, but the U.S. had the upper hand for most of the past decade.
The biggest American success came on neutral soil, in the 2002 World Cup finals in South Korea, where the two nations faced off in the last 16.
Goals by Landon Donovan and Brian McBride ensured a 2-0 win which sent Mexico home to much rancor and the United States into the quarter-finals, where they lost to Germany 1-0.
Mexico ended a run of five games without a win against the U.S - four of them defeats - when they crushed Bob Bradley's second string side 5-0 in the 2009 Gold Cup final and pride was further restored with a 2-1 victory in the Azteca Stadium, Mexico City in qualifying for last year's World Cup finals.
A win on Saturday would make it three in a row for the Mexicans and give them just cause to claim they are back at the top of the CONCACAF pecking order.
