United's prolific striker Ruud van Nistelrooy was once again the star, breaking the deadlock in the 46th minute after an evenly-fought first half.
The Dutch striker ran onto a flick from Uruguay's Diego Forlan and held off two defenders before slotting home a right foot shot from the edge of the penalty box.
"The way he scored the first goal is so typical and so quick and at such a high level that Ruud has to be one of the best and perhaps the best striker in the world," Club America's Dutch coach Leo Beenhakker said after the game.
The goal seemed to stir United into life and three minutes later Forlan himself extended the lead, heading home a cross from Quinton Fortune.
Club America appeared to have got back into the game in the 52nd minute when Alvaro Ortiz curled a beautiful free-kick into the top right hand corner of the net but American referee Ali Saheli disallowed the goal for a push.
Forlan capped a lively performance with his second goal in the 79th minute.
A long clearance by United goalkeeper Ricardo was flicked on by Ole Gunnar Solskjaer
Christian Patino scored a consolation goal for the Mexicans in the 87th minute.
Manchester United manager Alex Ferguson expressed satisfaction with his team's performance although his said the score was "perhaps a bit flattering".
"The making and the taking of the goals was very, very good," he said.
United began their tour with a 4-0 victory over Scottish club Celtic in Seattle.
"I don't think we looked as sharp as we did against Celtic ... Today we were playing against heat also," Ferguson said, noting the Seattle game had been in the evening while the Los Angeles match was played under the hot afternoon sun.
The game attracted a crowd of 57,365, many draped in Club America's canary yellow colours.
"I thought the atmosphere was absolutely fantastic. I think the blend of the Mexican and United fans added a competitive element to the match. I thoroughly enjoyed it," Ferguson said.
Ferguson said three members of his team were currently carrying injuries.
He told reporters that Gary Neville had a hamstring injury, Paul Scholes a groin injury and Roy Keane a thigh injury.