Nigerian international Idion ighalo inspired Manchester United to another impressive Premier League victory and deepened Aston Villa's relegation worries.
Ole Gunnar Solskjaer's side continued their impressive recent run, extending their unbeaten streak to 17 games in all competitions, and closed to within a point of fourth-placed Leicester.
The miss proved vital as the excellent Fernandes converted from the penalty spot after being tripped by Ezri Konsa, although it appeared to be a foul by the Portuguese international on the Villa defender.
United controlled the possession and tempo of the contest and doubled their advantage through teenager Mason Greenwood, who further highlighted his ruthless finishing ability by firing in his 16th of the campaign.
Paul Pogba stroked in a delightful third and Anthony Martial smashed against the crossbar, with the heavy defeat leaving Villa second bottom, four points adrift of safety with four games remaining.
Ighalo came on the 79th minutes to substitute goal scorer Anthony martial.