The world champion was only 5-hundredths of a second faster than McLaren's Lewis Hamilton, who sat out the final quarter hour of the session due to a minor technical issue.
Vettel won in Singapore last season but has won only one race this season, whereas Hamilton has taken the two most recent grand prix and looms as the greatest threat to championship leader Fernando Alonso.
Hamilton's teammate, Jenson Button, was third fastest as McLaren gave an early indication that it can handle the twisty layout of Marina Bay after winning the past two races at the faster Belgian and Italian circuits.
Ferrari's Alonso was fourth fastest — a second off the pace — on a track where he has twice won, while Pastor Maldonado of Williams was fifth and Mark Webber of Red Bull sixth.
The session began with the cars on intermediate tires because of a damp Marina Bay track caused by an afternoon thunderstorm, but slick tires were soon applied.
The Force India pair of Nico Hulkenberg and Paul di Resta finished seventh and eighth fastest respectively, while Toro Rosso's Daniel Ricciardo and Sauber's Sergio Perez rounded out the top 10.
Teams tried to quickly discover how to get the best out of new wings and parts, which are required given the big shift in racing styles between Monza and Marina Bay.
Mercedes has the biggest upgrade this weekend, using a new exhaust system that directs air onto the rear wing and rear diffuser to aid downforce and traction. Michael Schumacher was 14th and Nico Rosberg 18th, indicating the team has some way to go to find how to maximize the new setting.
Lotus' Kimi Raikkonen, who is third in the championship despite not having a race, was 13th.Suggest a correction