Further proof of the club's progress at youth level was displayed as Howard Wilkinson's starting line-up included no less than four Upton Park starlets.
Joe Cole and Michael Carrick, who stepped down from the senior squad after making their full debuts against Mexico last week, were joined by Jermain Defoe and Stephen Bywater - fresh from making their own debuts for the under-21 side, also against the Mexicans.
However, against a talented and clever Greek side, England's hopes of qualifying for the finals were severely dented as the hosts outplayed and outfought their opponents, racing into a two-goal lead before half-time.
With England on the back-foot from virtually the first whistle, Papadopoulos headed the opener on 26 minutes and Vakouftsis added a vital second just three minutes before the break.
With Cole prevented from creating by the strong-arm tactics of the Greeks and Carrick looking unusually subdued, England offered little going forward and Defoe was replaced by Arsenal winger Jermaine Pennant at half-time after an ineffective opening 45 minutes.
Things went from bad to worse 15 minutes into the second half, as Bywater embarrassingly let John Terry's unexpected back-header slip under his body and gift the Greeks an unassailable three-goal lead.
England then at last began to pile on some pressure of their own and Cole had a headed goal disallowed for offside before Carrick added some respectability to the scoreline with the best goal of the match just five minutes from the end, a scorching low shot from 25 yards out.
Sadly the latter stages of the match turned ugly as the England players, frustrated not only by the heavy tackling and blatant play-acting of the Greeks, but also the inability of the Russian referee to crack down on such behaviour, allowed their tempers to flare.
Cole, Ameobi and Prutton were all harshly booked, before the game boiled over completely in stoppage time. Tottenham defender Luke Young was sent off for pushing an opponent who had appeared to elbow him in the stomach, while Terry received his marching orders just moments later for a wild tackle on a Greek striker.
The trip to Athens will have been an awakening experience for the four young Hammers stars, who can now look forward to a well-earned rest before returning to pre-season training in July under a new manager at Upton Park.
Team: Bywater, Young, Naylor, Davis (Prutton 75), Terry, Upson, Carrick, Cole, Christie (Ameobi 73), Dunn, Defoe (Pennant 46).