The Mercedes driver lowered the lap record he had set around Istanbul Park in the first session with a one minute 23.804secs, beatring the Ferrari by 0.166s.
Valtteri Bottas beat both Red Bulls to third, 0.410s adrift of Hamilton after an hour of running where car balance was hard to find.
Max Verstappen finished fifth behind team-mate Sergio Perez after suffering from the same understeer that hampered his morning running.
Nicholas Latifi was the only driver to rotate his car at turn nine, making the mistake twice, although numerous others struggled to find their range at the same chicane with a tailwind ensuring picking a braking point was difficult throughout.
Lando Norris was one such driver to scamper across the run-off area at that location but recovered to set the sixth-fastest time on his second flying lap, whilst Alpine continued its form with Fernando Alonso and Esteban Ocon seventh and eighth.
Pierre Gasly's time of a 1:24.756s ensured the top nine had set a time faster than Juan Pablo Montoya's previous fastest lap of the circuit, with Antonio Giovinazzi fractionally slower to round out the top 10.
AlphaTauri driver Gasly did spin late on at turn six, moments after complaining that his "arms were too short" to cope with the understeer he was dealing with, whilst Nikita Mazepin was the first of the weekend to lose control at turn eight.
During medium tyre running, Leclerc was 0.099secs faster than Hamilton with Verstappen only seventh fastest, almost a second away.
There was some drama at the end of the session with Ocon stranded on the grid, failing to select a gear when attempting a practice start.
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