The Spaniard clocked an impressive time on the C4 tyres, setting a 1m17.144 and completing over a century of laps during the day.
Fellow McLaren driver Lando Norris also topped the timesheets on Tuesday, although caused two red flags during the session.
The times however will be encouraging for McLaren, who are yet to win their first grand prix since Brazil 2012.
Sergio Perez ended the day second quickest, also dipping into the 1m17s on the C4 tyres.
It was an impressive time from the Mexican, with Racing Point showing encouraging times on the second week of testing so far.
Vettel brings out red flag during morning session
Sebastian Vettel ended the session third fastest, going a second slower than Sainz using the C3 tyres.
The German caused a red flag during the morning session after going into the gravel at turn three, only completing fewer than 50 laps during the day.
Kimi Raikkonen managed to go fourth fastest in his Alfa Romeo, setting his best time on the C4 tyres, ahead of Romain Grosjean in fifth.
The Haas driver completed over 100 laps over the course of the day, although his best time, using the C5 tyres, was a tenth slower than the Finn’s time using the C4’s.
Max Verstappen ended the day sixth quickest using the C3 tyres, unable to replicate his team-mate’s time from Tuesday on the same tyre compound.
Pierre Gasly had managed to dip into the 1m17s, with Verstappen only able to set a 1m18.395, going three tenths quicker than Daniil Kvyat in seventh.
Mercedes up their pace
Mercedes improved their times from Tuesday, with Valtteri Bottas going eight quickest, with Lewis Hamilton behind in ninth.
The Silver Arrows upped their pace, setting times in the 1m18s on the C3 tyres, although could not match Ferrari’s best times.
Renault remained down the order, with Nico Hulkenberg going 10th fastest and Daniel Ricciardo the slowest of anyone, although throughout the morning the Australian had done race runs.
Robert Kubica split the two Renault drivers, going 11th fastest in his Williams.