Russell enjoyed a sunny and trouble-free afternoon as he lapped the Circuit de Barcelona-Catalunya with a fastest time of one minute 16.363 seconds, 0.203 quicker than McLaren's Oscar Piastri.
Ferrari's Charles Leclerc was third on the timesheets, 0.520 seconds slower than Russell, with Red Bull's Max Verstappen fourth and McLaren reserve Leonardo Fornaroli, taking world champion Lando Norris's car, fifth.
Other reserves in action included Paul Aron in an impressive sixth for Audi, Dino Beganovic at Ferrari, Ayumu Iwasa at Red Bull and American Colton Herta, a nine-time winner in IndyCar, at Cadillac.
Luke Browning had been due to take Alex Albon's Williams for the session, but failed to set a lap time due to an electrical issue. A second session followed later.
Barcelona hosts the seventh round of the season, with Antonelli chasing a sixth win in a row.