It was the Barcelona forward who made the biggest impact in a comfortable win, but he was left out of the starting lineup by Brazil boss Dunga.
Neymar's absence did not prevent the visitors from making an impressive start as Hulk broke the deadlock in just the ninth minute by firing home from close range after Willian's cross had struck the post.
Neymar was introduced before the start of the second half and he was immediately causing problems for the American defence as he collected an inch-perfect lobbed pass from David Luiz before being pulled down by Geoff Cameron in the box.
An emphatic penalty followed as Neymar powered his shot past the helpless Guzan to double Brazil's lead.
Brazil pulled further ahead three minutes later as Lucas registered his second assist by picking out Neymar, and the home defence were left paying for their mistake as he used the space on offer to cut inside and fire past Guzan with over 20 minutes remaining.
USA managed to pull a goal back in spectacular fashion when Danny Williams unleashed an unstoppable 30-yard strike in stoppage time, but his memorable goal proved to be no more than a consolation as Brazil celebrated a comfortable win.