Verstappen, chasing a record 16th win of the season and his fifth in the last six editions of the race, lapped the Autodromo Hermanos Rodriguez with a best time of one minute 19.718 seconds.
Williams' Alex Albon was second fastest, splitting the Red Bulls with a time 0.095 slower than Verstappen towards the end of the session. Perez was 0.297 off the pace.
Ferrari's Charles Leclerc was fifth and in a McLaren sandwich, with Lando Norris fourth and Oscar Piastri sixth fastest.
Carlos Sainz was seventh for Ferrari with Daniel Ricciardo eighth for AlphaTauri, with his car shedding some bodywork on the main straight.
Mercedes' Lewis Hamilton was only 11th but team boss Toto Wolff explained that by saying the seven times world champion had been testing various items with "lots of measurements on ride height and plank wear".
Hamilton was disqualified last Sunday in Texas for excessive wear of the plank under the car.
"Lewis made a mistake on his fast lap and would have been around about P2 or P3, so that's OK," added Wolff.
Five young drivers replaced race regulars for the session as part of a requirement for teams to give track time to rookies, with Britain's Ferrari Academy driver Oliver Bearman the highest placed in 15th for Haas.
Isack Hadjar was 17th for AlphaTauri, Jack Doohan 18th for Alpine, Frederik Vesti 19th for Mercedes and Theo Pourchaire 20th for Alfa Romeo after failing to set a flying lap due to brake issues.
Teams were also trialling Pirelli test tyres at times during the session, with teams reverting to normal set-up work after two successive sprint weekends with only one practice rather than the usual three.
