The reigning world champion ended more than half a second clear of the chasing pack, having improved his own benchmark several times over the course of the morning's running.
His ultimate best, a 1m22.197s, came after a late one-lap run on Pirelli's soft compound.
Lewis Hamilton, getting his first taste of the Mercedes W04 at Barcelona, was Vettel's nearest challenger despite being more than 0.529s down the road.
Hamilton's focus appeared to be longer runs on the hard tyre, and it was on the orange compound that he set his fastest lap and the outright best in the final sector.
Sergio Perez, the man who replaced Hamilton at McLaren, came within 17 thousandths of a second of the Briton's run following his own late soft-tyre run.
Perez's late rally pushed Ferrari's Fernando Alonso down to fourth, the Spaniard having set his outright best with more than an hour of the session to run.
On his first day in the Williams FW35, Valtteri Bottas was the morning's second busiest, and fifth fastest, driver.
The Finn managed 53 laps before Williams elected to stop early, its aero programme complete.
That was in stark contrast to Lotus and Kimi Raikkonen, whose morning was massively restricted by a gearbox change.
The Finn managed just four laps, none of them timed, just one day after speaking of his frustration as a data issue limited Lotus's mileage.
Less than one second covered Daniel Ricciardo, Paul di Resta and Nico Hulkenberg in the fight for sixth, with the Toro Rosso man eventually claiming the honours.
That left Charles Pic and Max Chilton bringing up the rear of the field, ahead of the stricken Lotus.
1. Sebastian Vettel Red Bull 1m22.197s 43
2. Lewis Hamilton Mercedes 1m22.726s +0.529 64
3. Sergio Perez McLaren 1m22.743s +0.546 35
4. Fernando Alonso Ferrari 1m23.247s +1.050 28
5. Valtteri Bottas Williams 1m23.561s +1.364 53
6. Daniel Ricciardo Toro Rosso 1m23.718s +1.521 46
7. Paul di Resta Force India 1m23.971s +1.774 41
8. Nico Hulkenberg Sauber 1m24.638s +2.441 39
9. Charles Pic Caterham 1m26.985s +4.788 52
10. Max Chilton Marussia 1m28.900s +6.703 32
11. Kimi Raikkonen Lotus - 4
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