The Sky team leader overtook Spain's Dani Moreno — the winner of last week's Fleche Wallonne — in a strong finish and crossed the line six seconds ahead of American rider Andrew Talansky.
Croatia's Robert Kiserlovski, was third, 13 seconds adrift of first place, while Australia's Richie Porte, a Sky team-mate of Froome, was fourth at 15 seconds.
"It was just seven kilometres but uphill, which is unusual for a prologue," Froome told Swiss television.
"I hadn't raced for a month, since the Criterium International (which Froome won) and I wasn't sure what kind of form I would be in.
"To win the prologue is a good sign and I hope to defend the leader's jersey for as long as possible this week but I know it will be difficult."
Wednesday's first stage is a 176.4-kilometre ride from St-Maurice in the canton of Valais to Renens, just outside Lausanne in the canton of Vaud, with the five-stage Swiss race concluding on Sunday.
Froome will be hoping to not only win here but go on like the winners of the past two editions, Australian Cadel Evans and Froome's Sky team-mate Bradley Wiggins, and win the Tour de France in the same year.
CYCLING
UK’s Froome wins Tour de Romandie prologue
Britain's Chris Froome, the pre-race favourite, on Tuesday won the Tour de Romandie prologue, a 7.4.kilometre bike race in French-speaking Switzerland between Chable and Bruson, in a time of 13 minutes 15 seconds.
Published: 23 April 2013 20:33 CEST
After winning the Tour de Romandie prologue, Chris Froome is kissed by hostesses. Photo: Fabrice Coffrini/AFP
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