Chasing his third straight win in Formula One's annual night race and seemingly headed for a fourth successive drivers' championship, Vettel set a time of 1 minute, 44.249 seconds on the Marina Bay circuit; six tenths of a second clear of teammate Mark Webber.
Mercedes drivers Nico Rosberg and Lewis Hamilton were the nearest rivals, but third-placed Rosberg was more than a second slower than Vettel.
"The time we set was a surprise today, I got a good lap in, but I don't think it's completely representative," Vettel said. "We seem to be quick, but Mercedes will be very strong in qualifying tomorrow."
Lotus driver Sebastian Grosjean had steering problems in the early session and a hydraulic failure in the late one, but was still fifth quickest, outperforming his more experienced teammate Kimi Raikkonen in eighth.
Ferrari's Fernando Alonso — who reiterated his commitment to the team on Friday amid speculation of a move to McLaren — was sixth, ahead of McLaren's Jenson Button. Force India's Adrian Sutil and McLaren's Sergio Perez were ninth and 10th.
There were few incidents over the two 90-minute sessions. Williams' Pastor Maldonado went nose-first into one of the concrete barriers that hem the street circuit but the car had only minor front-wing damage.
The lack of problems was a testament to both the track surface, which has more grip this year after resurfacing, and the concentration of drivers who must go through 78 gear changes per lap on the twisty circuit, while dealing with the intense heat of driving under floodlights in the tropical climate.
Vettel's performance was dispiriting for his rivals, who need a dip in the German's imperious form if they are to reel in the already-comfortable 53-point lead he holds in the championship.
Should he top the times in Saturday's qualifying, that lead is likely to be extended further as Vettel has converted his past three pole positions this season into race wins.
About the only bad news for Vettel on Thursday was a 200-euro fine for speeding in the pit lane in the first practice session.
The yawning one-second gap between Vettel and third-placed Rosberg was a surprise, given that Mercedes had hoped that a return to a tight, high-downforce circuit would negate the speed advantage Red Bull enjoyed in Belgium and Italy.
Mercedes had taken the pole-and-win double at both Monaco and Hungary, the two other races with comparable race settings.
"There are some big gaps on the timesheets but we need to focus on our own program and not get distracted by what our competitors are doing," Mercedes F1 executive director Toto Wolff said.