Brittain created the controversial E4 show with dad Bryan Elsey in 2007, and has written for it since its inception.
But on Friday he announced he was quitting, telling website AfterEllen: 'I've just said everything I wanted to say. It's time for new writers to come forward and portray their truth about teenagers.
'I'm really sad to leave, but I'm confident that the writing and production team I've left behind will do an awesome job.'
Brittain's departure leaves the show without any of its original creators, after Elsey left to work on the US remake at the end of series four.
And while series six has already been commissioned and will still go ahead, the long-term future of the show looks doubtful.
Series five experienced a drop in ratings after receiving a very mixed critical reception, leading many to question whether the show has passed its peak.
With the cast due to be changed at the end of the next series, there is a strong chance the sixth series could be the show's last.
A Channel 4 spokesperson refused to be drawn on the long-term future of the series, telling Metro.co.uk: 'Jamie has decided after five hit series to move on to write new projects and we wish him well.
'Skins is written by a team of young writers who are hard at work on the new series which is currently in pre-production.'
Brittain himself has emphasised he isn't 'abandoning' the show, writing on his Twitter page: 'Not abandoning it. It's just time for me to go.'
The show will now be left in the hands of current assistant producer Toby Welch and script producer Neil Duncan, and Brittain has assured fans series six will be 'great.'