Leclerc will not be a contender for pole position on Saturday at Interlagos, as he will serve a 10-place grid penalty for taking a new engine, but his and Vettel's form bodes well for the Scuderia.
Vettel took P1, despite seeing his initial single-lap run interrupted by Valtteri Bottas, who also got in the way of his Mercedes team-mate Lewis Hamilton in a clumsy session.
The Mercedes were narrowly behind the Red Bull of Max Verstappen in one-lap trim.
Robert Kubica started the session in dismal fashion, taking a trip into the barriers exiting the Senna esses on his first meaningful lap of the session, having sat out FP1 as Nichols Latifi took over, while the session also ended under the red flags after Daniil Kvyat crashed and his Toro Rosso caught fire.
Qualifying is set to be fraught, with positions seven to 18 separated by just half a second on the short runs.