Rooney came on in the 58th minute for his 120th and final England appearance, with the 33-year-old raising money for the Wayne Rooney Foundation in the international friendly.
Rooney was presented with a plaque ahead of kickoff as he took to the field alongside wife Coleen and his four boys. There was to be no goal for the DC United attacker, however, with Jesse Lingard, Trent Alexander-Arnold and debutant Callum Wilson those on the scoresheet for Gareth Southgate's side.
Wilson had the first half-chance of the match in the ninth minute, but the Bournemouth forward could not made proper contact on a cross from Lingard.
Wilson was involved in a penalty shout moments later when he went down under a challenge from USA goalkeeper Brad Guzan, but the referee was not interested despite the clumsy nature of the contact.
Lingard then tested the reactions of Guzan with a powerful strike in the 13th minute as England looked to make the most of their early domination.
Less than one minute later, England took the lead. The Three Lions continued to have joy down the left, and Dele Alli cut inside before finding Lingard, who bent an excellent effort into the top corner of the net.
The Three Lions then doubled their lead in the 27th minute when Jadon Sancho's clever pass found Alexander-Arnold, and the right-back's powerful strike flew past Guzan to stun the visitors once again.
USA were having their moments in the final third, but looked increasingly shaky at the back, with Sancho, Alli and Lingard having a lot of joy in the positions behind Wilson.
Julian Green tested Pickford from distance in the 36th minute, before Guzan had to keep out an effort from Wilson down the other end during an open period of the match, but there were to be no more goals in the first period.
Lingard poked an Alexander-Arnold cross wide of the USA post early in the second half as England, who introduced Southampton goalkeeper Alex McCarthy at the interval, looked for a third.
USA had a super chance to register in the 66th minute when Pulisic found the head of Bobby Wood from a short corner, but the forward's effort was just too high.
Rooney then curled one into the arms of Guzan in the 72nd minute, before Wilson turned a low Alexander-Arnold cross wide of the post 15 minutes from time.
England did have their third in the 77th minute, however, and it was a debut goal for Wilson, who turned a low Fabian Delph cross into the back of the net to cap an excellent performance from the centre-forward.
Rooney was heavily involved in England's work late on as he looked to bow out with a goal, but Guzan kept out a low strike from the nation's all-time record goalscorer in stoppage time, before he just failed to meet a cross from Alexander-Arnold as the hosts declared at three.
ENGLAND (4-3-3): Pickford (McCarthy 46'); Alexander-Arnold, Keane, Dunk, Chilwell (Dier 58'); Delph, Winks (Loftus-Cheek 70'), Alli (Henderson 58'); Lingard (Rooney 58'), Wilson (Rashford 79'), Sancho
USA (4-2-3-1): Guzan; Yedlin, Miazga, Brooks, Villafana (Moore 88'); McKennie (Lletget 76'), Trapp (Acosta 70'); Pulisic, Green (Adams 62'), Weah (Saief 76'); Wood