Wales have not won at Twickenham in 20 years and Gatland is leaning heavily on the Ospreys' recent success against English clubs.
The big-spenders from the Liberty Stadium have beaten Gloucester, London Irish, Harlequins and Worcester this season to reach the last eight of the Heineken Cup and the EDF Energy Cup semi-finals.
The last time one club was so heavily represented in the national team was 60 years ago, when Cardiff dominated the Wales line-up.
Gatland's first Wales squad also includes the surprise selection of Sonny Parker ahead of Tom Shanklin at outside centre.
As expected, James Hook is preferred to Stephen Jones at fly-half while Gavin Henson will make his first start in the Six Nations since the 2005 Grand Slam campaign.
Gatland said: "We want to stress that this is very much a 22-man selection, we have an extremely strong bench to call upon with three former British Lions in there if we need them.
"We haven't gone out to pick as many Ospreys as possible by design, the fact that there are 13 of them is probably more of a coincidence than anything else, but saying that you can't escape the fact that they've been one of the form sides in Europe so far this season."
Lee Byrne won the battle to start at full-back, while Mike Phillips dons the scrum-half jersey with Dwayne Peel nursing an ankle injury.
"Dwayne Peel was ruled out of selection for this week due to an injury he picked up in training to his right ankle, but we hope to have him back in contention for next week," added Gatland.
"Dwayne's injury gives Mike a chance to perform and James completes that partnership with Stephen Jones, having not played much rugby recently, taking up a place on the bench.
"We have been impressed with Lee Byrne in defence for the Ospreys and his confidence under the high ball in training and positional play has given him the nod at full-back."
The big decision in the pack was in the second row, where Ian Gough starts alongside Alun-Wyn Jones with Ospreys team-mate Ian Evans on the bench.
Ryan Jones will captain Wales for the first time having won both his previous matches against England.
Wales team to play England in the RBS 6 Nations Championship at Twickenham on Saturday:
L Byrne (Ospreys); S Williams (Ospreys), S Parker (Ospreys), G Henson (Ospreys), M Jones (Llanelli Scarlets); J Hook (Ospreys), M Phillips (Ospreys); D Jones (Ospreys), H Bennett (Ospreys), A Jones (Ospreys), I Gough (Ospreys), AW Jones (Ospreys), J Thomas (Ospreys), M Williams (Cardiff Blues), R Jones (Ospreys, capt).
Replacements: M Rees (Llanelli Scarlets), G Jenkins (Cardiff Blues), I Evans (Ospreys), A Popham (Llanelli Scarlets), G Cooper (Gloucester), S Jones (Llanelli Scarlets), T Shanklin (Cardiff Blues).