Roberto Martinez's side had already qualified for Euro 2024 during the previous international break in October, but were no less fierce, taking the lead after just five minutes through a Cristiano Ronaldo penalty.
Ronaldo added his second 15 minutes later, chipping Joao Felix's intricate pass over Ibrahim Sehic to double the lead.
Mere moments after the second goal, Fernandes made it three by controlling Goncalo Inacio's through ball with his chest before hitting an unstoppable volley into the top corner from inside the box.
The United captain then turned provider for a sublime Joao Cancelo finish, cutting it to the edge of the box for the Barcelona man to curl into the top corner.