Karmarama has won the account after a three-way pitch that included Wieden & Kennedy and TBWA. Bartle Bogle Hegarty was asked to pitch at an earlier stage but pulled out of the review in January.
The incumbent, Publicis London, did not repitch for the account, which Confused.com said is worth £40 million.
Confused.com described Karmarama as a "wild-card entry" in the pitch process, which began earlier this year, despite having previously referred to TBWA as the "wild card".
The review followed the arrival of a new chief marketing officer, Paul Troy, who created the "you’re so Moneysupermarket" campaign with Mother when at the brand from 2011 to 2013.
Troy said: "These are exciting times for Confused.com and this is just the start of a wave of new activity planned for this year to re-energise our brand and drive market share growth.
"We have big plans for Confused.com and Karmarama are a great creative partner to help us realise that ambition."