The show - which made worldwide stars of Courteney Cox and Jennifer Aniston - continues to be a nightly staple of the broadcaster's digital channel E4, despite ending almost six years ago.
C4 said that ending the deal next year will - together with the end of Big Brother - free up more cash for original programming and US buy-ins.
The station has agreed with Warner Bros - the programme's distributor - to end its rights to the series in the autumn of 2011.
Friends became a massive ratings hit for the channel as viewers became hooked on the antics - and varying hairstyles - of Rachel, Phoebe, Chandler, Joey, Ross and Monica from 1995 onwards.
The last ever episode from series 10 drew an audience of 8.6 million viewers when it was screened in 2004.
E4 still shows the programmes seven nights a week and draws an average of almost 400,000.
Channel 4 said the decision would allow it to "refresh the schedule" on the main station and on E4.
Gill Hay, head of acquisitions, said: "After 15 years, 10 hit series and 236 terrific episodes it's time to say goodbye to old Friends and welcome new ones, in the form of more comedy, drama and entertainment from the US and UK. We are incredibly proud to have been the home of Friends for so long, but at a point when the channel is undergoing a period of creative renewal it felt like the right time to part company."