The Mexican, among the favourites for pole position, edged out team mate Max Verstappen (24), who is facing a grid drop from power unit and gearbox-related penalties, with a one minute 45.047 second lap.
Ferrari’s Carlos Sainz (27) was third but nearly a second off the pace as Red Bull continued to display a dominant turn of speed, around a cold and overcast Spa-Francorchamps.
Verstappen, who came under investigation for failing to slow down for yellow flags, leads Ferrari's Charles Leclerc (24) by 80 points in the overall standings with nine races remaining.
Leclerc has not given up hope but, like Verstappen, is set to line up at the back of the grid after also collecting power unit and gearbox-related penalties.
The pair are among seven drivers facing similar grid drops.
Lando Norris was fourth for McLaren ahead of Alpine's Fernando Alonso, George Russell in a Mercedes and Leclerc, who had a spin into the barriers.
Aston Martin's Sebastian Vettel complained of power unit problems but was eighth fastest ahead of Esteban Ocon's Alpine. Pierre Gasly rounded out the top 10 in his AlphaTauri.
