Aura Sports will sell advertising and sponsorship packages across the websites for West Ham, Southampton, Leeds United, Manchester City and Sunderland.
The agency already represents Chelsea Digital Media, the joint venture between Chelsea Football Club and Sky, in a deal made last month.
Sky had handled the advertising sales and sponsorship functions for the six clubs in-house. It still handles the work for Tottenham Hotspur.
The move means Aura Sports has now muscled in on the football advertising sales market dominated by a handful of big players including Granada, which has joint ventures with the heavyweight clubs Liverpool and Arsenal, and ntl.
The farming out of the work by Sky to a specialist agency is recognition of the increasing importance of digital revenues to clubs, particularly Premier League clubs, which have enormous advertiser and revenue opportunities in largely untapped fan bases outside of the UK market.
"We will add commercial revenue and partners for clients," Paul Wright, the managing director of Aura Sports, said. "Sport doesn't lend itself a network sales approach that the likes of Real Media and AdLINK offer."