The 32-year-old Perez from Guadalajara, Mexico, benefitted from an executed pit strategy to lead the final 44 laps and fend off Carlos Sainz for his first victory at Circuit de Monaco.
The reigning Formula 1 champion led 24 of 66 laps before completing a late overtake and fending off teammate Perez for his second Grand Prix victory in Spain.
The 24-year-old Dutchman took another swing towards Charles Leclerc's championship lead by claiming his third victory of 2022 and his first in F1's inaugural Miami GP.
The 24-year-old Monegasque driving for Ferrari extended his lead in the drivers' championship standings after claiming a dominant victory in Melbourne's Albert Park Circuit.