Hamilton, runner-up in Valencia for the third year in a row, still managed to double his championship lead over Button, who finished third.
On a hot afternoon full of incident and controversy, and at a street circuit that has offered few thrills in the past, Vettel charged back into the championship reckoning with his second win of the season.
Hamilton, who had started the day three points clear of his team mate, now has 127 points to Button's 121 after nine races, with Vettel on 115.
"It's about time," said the German, who had failed to convert his three previous poles this season into victory but found himself celebrating a double victory over the English after Germany thrashed England 4-1 in the World Cup.
"It is good to be back and on a circuit where we didn't expect to be that strong, to be quick enough all the time in the race to slightly pull away, find the gap and then carry the car home. It wasn't as easy as expected."
While Vettel sprayed the champagne, teammate Mark Webber could have used a gulp of something stronger after providing the day's big drama when he walked away unscathed from a massive crash on lap 10.
The Australian's car was launched vertically into the air after slamming into the back of Heikki Kovalainen's Lotus, the Red Bull twisting in the air and landing upside down on the nose and roll bar.
"I was worried about any bridges or things that I could hit in the air," said the Australian, who had already endured a nightmare first lap, with barely a flicker of emotion. "I knew I was a long way up."
Former Red Bull driver David Coulthard said his ex-teammate had been fortunate: "Motor racing has just seen one of its luckiest days. That could have been a very, very bad incident."
The safety car was deployed for four laps after Webber's accident, triggering a drive-through penalty for Hamilton, who was judged to have illegally overtaken it at the pit lane exit.
To the fury of Ferrari's Fernando Alonso, who was immediately behind and found himself held up by the safety car, Hamilton had built up a sufficient margin that he was able to take his penalty and still retain position.
"It's a pity for us...and the 60,000 or 70,000 spectators who came here and saw a manipulated race," Alonso told Spanish reporters.
The drive-through, on the 27th of 57 laps, took the sting out of what might have been an enthralling battle at the front as Hamilton chased his third win in a row.
He had banged wheels with Vettel on the opening lap after barging past Webber for second place but crossed the line 5.042 seconds adrift of the winner.
"I tried my best and at the end it was just looking after the tyres and bringing the car home," said Hamilton.
Alonso finished ninth in front of his home crowd but moved up to eighth after nine drivers including Button were handed five-second penalties by stewards at a post-race enquiry for breaching safety car regulations.
Brazilian Rubens Barrichello, last year's winner for champions Brawn GP, finished fourth for Williams with Poland's Robert Kubica fifth in a Renault.
Germany's Adrian Sutil was sixth for Force India ahead of Sauber rookie Kamui Kobayashi, who completed all but the last four laps on one set of tires and was running as high as third.
The Japanese passed Alonso on the last lap and then Sebastien Buemi's Toro Rosso into the final corner.
The five-second penalty demoted Buemi to ninth while Germany's Nico Rosberg moved up to 10th place at the expense of Spaniard Pedro de la Rosa in the second Sauber.
Germany's seven-times champion Michael Schumacher finished 15th for Mercedes.
