The Monegasque driver made the most of his heavily-revised package while championship leader and three-time champion Max Verstappen struggled for his usual Red Bull performance.
Leclerc clocked a best lap in one minute and 15.906 seconds to ease 0.192 clear of nearest rival Oscar Piastri of McLaren with RB's Yuki Tsunoda snatching third in a closely-bunched pack at the front of the field.
It signalled a successful first day for Leclerc's partnership with new race engineer Bryan Bozzi.
Seven-time champion Lewis Hamilton was fourth ahead of team-mate George Russell and Carlos Sainz in the second Ferrari, leaving an exasperated Verstappen back in seventh ahead of team-mate Sergio Perez.
Nico Hulkenberg was ninth for Haas and two-time champion Fernando Alonso 10th for Aston Martin on a day when most drivers had struggles with the windy conditions.
Verstappen went off and detoured through gravel traps three times in all while Hamilton and Sainz were also seen spinning and taking unscheduled excursions.
Earlier, on a beautiful, dry sunlit afternoon at the Autodromo Enzo e Dino Ferrari, Verstappen swiftly took control with a lap in 1:16.930 – a major improvement after his earlier struggles in FP1 – to go top ahead of Norris, Leclerc and Sainz.
"Yeah, much better," he reported to engineer Tom Hart, who had taken over from Gianpiero Lambiase for the day. "A lot better on this tyre now.3
Seeking to shine at his team's true 'home’ circuit, just 50 kilometres from their Maranello base, Leclerc went top after 14 minutes for Ferrari, on mediums, and then improved by trimming his time to 1:15.969 on softs.
That lifted him half a second clear of Sainz, his team-mate, to the joy of most of the impressive Friday crowd of 'tifosi' enjoying the red cars' performance.
After half of the hour's action, Piastri went second, splitting the Ferraris with a lap just 0.129 seconds off Leclerc's pace before Russell went third, making it three different teams at the front – and Red Bull struggling to join them.
At this stage, Verstappen was sixth and Perez seventh before improvements from Tsunoda and Hamilton pushed them further down the order.
"My god, I don't know man. It's so difficult. Everything. This time, suddenly, the front grips a lot and I almost spin," exclaimed Verstappen as he gesticulated at a dawdling Hamilton.
For the champion, it was a day to forget, but Red Bull have shown many times that they have the resources to bounce back on Saturday and make a significant improvement in qualifying ahead of Sunday's race.
