Second in a first practice session led by teammate George Russell, Antonelli then set the pace in Friday's later session, which was halted briefly by Racing Bulls' British rookie Arvid Lindblad becoming the first F1 driver to crash and bring out the red flags at the new Madring circuit.
Antonelli's best lap of one minute 33.662 seconds was 0.113 quicker than Leclerc's fastest effort. Seven-times champion Hamilton was 0.149 off the pace with Lindblad fourth despite the crash ending his session with 24 minutes to go and Russell fifth.
It was another underwhelming day for Oscar Piastri, who was eighth quickest in the first session and seventh fastest in the second, while his McLaren teammate Lando Norris was sixth in first practice before sitting out the later action as the team changed his car's gearbox.
Teenager Lindblad apologised after losing control of the rear of the car and smashing into the barriers sideways at Turn 13.
Leclerc and Hamilton had been third and fourth in the first session at a bright and sunny Madring, a challenging track that runs around the IFEMA exhibition centre near the capital's Barajas airport.
After a fiery crash halted the earlier F2 practice, the opening Formula One session took place without interruptions or major incident.
Home hero Fernando Alonso brushed the wall in his Aston Martin and was 15th and 17th in the sessions respectively, while Spain's other driver Carlos Sainz was 17th and 16th for Williams in his home city.
There were complaints from several drivers over the radio about others getting in the way.
"That's just nasty," exclaimed Hulkenberg after Hamilton failed to let the German through at the final corner.
Lindblad also called out Hamilton and Antonelli as "stupid" after accusing them of obstruction at the circuit's signature 'La Monumental' banked turn 12.
