With sunshine replacing the morning's drizzle, when Alonso was top of the timesheets with a largely meaningless lap of one minute 25.252 seconds on a drying track, Vettel produced a quickest time of 1:22.808.
Alonso was second, 0.017 slower, with Australian Mark Webber third with a best lap of 1:22.891.
Qualifying has been critical at the Circuit de Catalunya in the past, with 18 of 22 winners there to date starting on pole position and all but one - Michael Schumacher from third in 1996 - from the front row of the grid.
McLaren's Jenson Button failed to set a lap time in the damp first session, with the team opting for caution in the knowledge that they have a limited number of spares for their new aerodynamic upgrade package.
The 2009 world champion was 12th after lunch with a best effort of 1:24.306 while Mexican team mate Sergio Perez lapped in 1:24.854.
"We've got enough parts for two cars, but we're limited on spares so we'd like to avoid crashing or going into gravel," explained McLaren sporting director Sam Michael.
Plans to provide more track action in the first session by giving drivers an extra set of prototype long-lasting hard tyres were stymied by the weather, with leaden skies and drizzle replacing Friday's sunshine.
Felipe Massa was just behind his team mate in 1:25.455 in a Ferrari one-two in that session and was fifth in the afternoon with Lotus's Kimi Raikkonen - a previous winner in Barcelona with McLaren and Ferrari - fourth.
Vettel, the overall championship leader who is 10 points clear of Raikkonen after winning two of four races so far, was 19th quickest of the 22 cars in the morning after waiting until the track was drying before venturing out for a proper lap. Webber was 20th.
All teams have updates for the first race of the European season but former champions McLaren and Williams - last year's winners with Venezuelan Pastor Maldonado - have more riding on them than most after struggling in Asia and the Middle East.
Button, the 2009 world champion, has finished no higher than fifth so far this season after winning the final race of last year in Brazil with what was then deemed to be the fastest car.
McLaren, who brought out a significantly new car this season instead of the more evolutionary approach favoured by others, have been working overtime to fix the aerodynamic problems with the team using one of their two 'jokers' for the season so mechanics could break an overnight curfew.
"It looks nice. There's some really cool looking little bits on the car but I don't think it's going to be enough to really fight right at the front," said Button before practice. "I think we will see an improvement and hopefully that will help us understand the air flow of the car a little bit better."
"If we get a good correlation between this circuit and the wind tunnel, that's just as important as seeing an improved lap time this weekend."