Profero won a four-way pitch, which was led by Tracy Blacher, Channel 4's head of marketing for new media.
The agency will be responsible for the online media for Channel 4, E4, FilmFour and More4, as well as the promotion of all Channel 4's new-media content and services.
New media, previously handled by OMD Digital on an ad-hoc basis, has become an integral part of Channel 4's strategy since Andy Duncan became the chief executive of the broadcaster last June.
Duncan has committed the station to developing its online and mobile channels. Channel 4 recently launched FourDocs, an online documentary channel available on broadband, and it has also revamped its portal.
Profero will work on the launch of More4, Channel 4's digital channel for the over-35s, alongside DDB London, which was appointed in April to handle the creative task.
Blacher said: "Profero was chosen because of its collaborative attitude, creative approach and enthusiasm. These are balanced with strong evidence of accountability."
Wayne Arnold, the managing director of Profero, said: "Our work for Channel 4 will reflect our reputation for providing cutting-edge and innovative solutions."
Profero will also work alongside OMD UK, which is Channel 4's above-the-line planning and buying agency.