The Americans maintained their perfect record in Group A to secure a spot in the final phase of North American qualifying, where three berths in South Africa will be decided. The Cubans lost their fourth successive game, all but ending their hopes of progressing.
Beasley opened the scoring in the 10th minute. The Glasgow Rangers star took a pass from Sacha Kljestan, outraced a defender on the left side of the penalty area and side-footed the ball past Cuban goalkeeper Odelin Molina.
Beasley scored again in the 30th minute, beating Molina from 10 metres out, but the Cubans answered seconds later, Jenzy Munoz finding the goal early in the 32nd minute. Munoz lofted a chip from just beyond the penalty area that grazed the bottom of the goalpost and dropped in, shocking a crowd of 20,293 at RFK Stadium.
Helpless USA goalkeeper Tim Howard of English Premier side Everton could only watch the ball fall across the line, the first goal conceded by the Americans in six FIFA World Cup qualifying matches this year.
But Cuban hopes dimmed in the 42nd minute when midfielder Yoel Colome fouled Landon Donovan to draw his second yellow card of the match and an expulsion, leaving the Caribbean side with ten men.
Donovan nearly struck in the 44th minute, chipping across the front of the goal, and then found the net in the 48th minute from point blank range to give the Americans a 3-1 edge. Brian Ching added a goal in the 63rd minute and Jozy Altidore, of Spain's Villarreal, netted another in the 87th minute. USA defender Oguchi Onyewu finished the scoring in the 90th minute to complete the rout.