Upstart, which was set up to appeal to smaller clients with limited budgets, won the business following a pitch against a number of unnamed agencies.
It has been briefed to work on the launch of a new show, Drake & Josh.
Nickelodeon is the agency's first piece of exclusive business. Upstart is also working on a project for the TBWA\London client Eurostar.
The senior marketing manager at Nickelodeon, Sarah Mieran, said: "Drake & Josh is an exciting addition for us which requires energetic and creative marketing. We are looking forward to working with Upstart because it provides the best of both worlds - small-agency dedication plus big-agency talent."
The last agency to work on the Nickelodeon account was Mustoes, which ran a TV, cinema and print campaign to promote the brand as well as specific programmes last July. It ended its relationship with the channel last year.
In February, Walsh Trott Chick Smith was hired to work on the Nick Junior channel.
Andrew Stirk, the director of TBWA\Upstart, said: "Nickelodeon has a credibility among children that no-one else can match. This is an amazing opportunity to produce some daring work for an audience that is actively looking to be entertained."
Andrew McGuinness, the chief executive of TBWA\London, added: "This is a major win for a brand-new venture.
"Nickelodeon is a premier-league brand that needs a highly focused, creative offer. That is exactly what Andrew and the TBWA\Upstart team will provide."