Substitutes improved upon the 3-1 advantage, with Esteban Granero putting away a Kaka pass in the 89th minute, and usual starter Sergio Ramos burying a header off a Kaka corner kick in the 82nd.
The Spanish club showed off its superior depth, turning a 1-1 score at halftime into a runaway victory.
"There is a big gap between us and Real Madrid for the time being," said AC Milan manager Massimiliano Allegri. "We played them good in the first half, but we suffered in the second half and let them play too much. We basically let them score three easy goals."
Ronaldo's were the result of strong finishing, though.
The Portuguese international star started the scoring four minutes after the half, burying a through ball from Lass Diarra that left Milan goalkeeper Marco Amelia flat-footed.
Seventeen minutes later, Ronaldo struck again. Substitute Gonzalo Higuain stole the ball deep in Real Madrid's own territory, then carried it up the wing and found Kaka in the middle of the field. The Brazilian turned and played a ball into the box for Ronaldo, who slid it to the far post and past the outstretched hand of Amelia.
"We were a phenomenal team before, and now we're not the worst team in the world," Allegri said. "We need to take and find the confidence in ourselves, and we need to face this kind of defeat."
Mourinho said his decision to play Ronaldo as much as he did was partially to appease the crowd, and partially to prepare for the season, which begins after one more preseason match Saturday as part of the World Football Challenge.
He played star goalkeeper Iker Casillas -- Real Madrid's version of Derek Jeter, the captain who starred in two European titles before he turned 21 -- 84 minutes, though he was rarely challenged and beat only once by AC Milan forward Robinho.
Mourinho started the likes Karim Benzema, Mesut Ozil, Sami Khedira and a very active Fabio Coentrao, then subbed them out in favor of Kaka, Higuain, Xabi Alonso and Ramos.
"That's life in Real Madrid. The squad is good," said Mourinho, who once brought his son to Yankee Stadium to marvel at its history. "Players coming from the bench are no worse than the players on the pitch."
The clubs soaked in the atmosphere, which Mourinho likened to the 85,000-seat capacity Estadio Santiago Bernabeu in Madrid, which they call home. Players posed with the interlocking New York logo behind home plate prior to kickoff, and Casillas and AC Milan captain Massimo Abrosini joined Yankees closer Mariano Rivera at midfield for the pregame coin toss.
The crowd quickly became vocal, starting the wave only five minutes in, then truly coming to life once Ronaldo found the ball at his feet.
"I think we did what the Stadium deserved," Mourinho said, "what Yankees history deserved."