The agency was appointed after a four-way shoot-out against JWT London, VCCP and CHI & Partners.
The incumbent, Beattie McGuinness Bungay, did not repitch.
Karmarama joins the Molson Coors roster and will start work immediately on an integrated campaign to launch in spring 2014.
Lord Bilimoria, a founder of Cobra, said the campaign aims to position the brand at the top of the UK lager category by celebrating its "impossible smoothness".
Molson Coors spends £2.4 million on UK media for Cobra, according to Nielsen. This is expected to increase to above £3 million for the coming year.
Last year, Cobra launched the "Cobra train" campaign, created by BMB, showing a train travelling through the Indian landscape.