Eric Miller was central to Ireland's first points after six minutes, taking up an initial drive from debutant Denis Leamy to draw an offside and offer Humphreys his first shot at the posts.
With Tom Billups' visitors not breaking into Irish territory until the 10th minute, Ireland were given a degree of latitude with both Paul O'Connell and the recalled Kevin Maggs prominent ball carriers.
Mike Hercus failed to punish Leamy's high tackle after 13 minutes, missing his first penalty attempt to the left but the former Australia Under-21 player did level with a second 30-metre effort four minutes later.
Humphreys smartly replied for 6-3 two minutes later before centre Shane Horgan eventually put Miller in past Treviso lock Gerhard Klerck - one of only four European-based professionals in the Eagles side - at the right corner.
Humphreys converted to push Ireland 13-3 clear but the visitors fronted up.
Just 13-6 up at the break, an expansive Ireland opened the second half with a try after 50 seconds through Murphy. The Leicester Tiger danced easily around Francois Viljoen to set the try-fest rolling.
O'Driscoll set Murphy up again for a right-wing dash to the line after 55 minutes and three minutes later 20-year-old Bowe crowned his first start with a try - darting past Al Lakomskis for the left corner.
Close-range drives from Munster duo Horan and Sheahan - both notching their second international tries on rare starts - tallied up the Irish points and substitute Stringer sniped over on the right in injury time to put a gloss on the scoreline.
Ireland: G Murphy; S Horgan, B O'Driscoll, K Maggs, T Bowe; D Humphreys, G Easterby; M Horan, F Sheahan, J Hayes, D O'Callaghan, P O'Connell, S Easterby, D Leamy, E Miller.
Replacements: S Byrne, S Best, L Cullen, A Foley, P Stringer, R O'Gara, G Dempsey.
USA: F Viljoen; A Lakomskis, P Emerick, S Sika, D Fee, M Hercus, M Timoteo, M McDonald, M Wyatt, J Waasdorp, A Parker, G Klerck, B Surgener, T Petruzzella, K Schubert(captain).
Replacements: M Hobson, C Osentowski, J Gouws, F Mo'unga, D Williams, M Sherman, A Tuipulotu.