The Monegasque driver, who was called afterwards to see the stewards for a potential infringement, clocked a best lap in one minute and 11.265 seconds to outpace nearest rival Valtteri Bottas of Mercedes by just 0.053 seconds.
His lap ended the Silver Arrows domination after they had topped both sessions on Thursday in cooler conditions.
Championship leader and defending five-time champion Lewis Hamilton was third in the second Mercedes, two-tenths adrift, ahead of Max Verstappen and his Red Bull team-mate Pierre Gasly.
Antonio Giovinazzi was sixth for Alfa Romeo ahead of Daniil Kvyat of Toro Rosso, Kevin Magnussen of Haas, Kimi Raikkonen in the second Alfa and Alex Albon in the second Toro Rosso.
On a mixed day for Ferrari, Leclerc's teammate four-time champion Sebastian Vettel crashed at the first corner after only 18 minutes. He was unhurt, but unable to run in the remainder of the session, leaving Ferrari with emergency repairs to the front suspension before the later qualifying.
The Mercedes cars ran with red Halo cockpit protection devices carrying the message 'Niki we miss you'.
On another hazy morning with warm sunshine filtering through the clouds, British rookie Lando Norris was first out on track in his McLaren followed the the most experienced man, Kimi Raikkonen of Alfa Romeo, in his landmark 300th Grand Prix.
After a cautious start, the Mercedes team were soon on top with Bottas and then Hamilton, after a brief Virtual Safety Car (VSC) period when Vettel locked up and ran into the barriers at Ste Devote.
"Front left's gone," he told Ferrari before apologising. His car was lifted out of danger and out of the session, ending Vettel's final practice after only 18 minutes and condemning him to the 'walk of shame' back to the pits, his red Niki Lauda tribute helmet, shining.
This was a serious blow to the 'scarlet scuderia' and piled more pressure on local hero Monegasque Charles Leclerc who was under investigation for a VSC infringement as Bottas went quickest again by one-tenth.
Leclerc then produced a best lap in 1:11.265 to go top, 0.073 ahead of Bottas, immediately taking tension out of the body language in Ferrari's garage before his post-session visit to the stewards' office.
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