GB knocked off their world-ranked No.9 opponents at home last November but it was a tougher mission in Larissa with a slick Greek team coming from behind to record a 93-71 win.
A third-quarter burst from the home side ended the hopes of a new-look GB after they had started positively with a 12-1 run.
Qualification for the Second Qualifying Round of the competition is already secured, but the significance of the upcoming fixture against Turkey - again in Newcastle on Sunday - is no less important as results for each team carry over.
Veteran Teddy Okereafor's record run of 51 consecutive appearances was brought to a halt as a rare injury forced him to sit out. But debutant Patrick Whelan made his presence felt in the opening quarter with five early points, as GB made a strong start to lead 20-19 at the first break.
A tit-for-tat second saw Greece take a 39-38 lead into the third, when they turned the screw with slick ball movement, accurate shooting and defensive pressure to hold GB to just 10 points while hitting 30 of their own to take a 69-48 advantage into the final period.
GB kept fighting in the fourth but the damage was done.
Hesson led the GB scoring with 23 points with Carl Wheatle (15) and Whelan (12), impressive in the backcourt, and Gabe Olaseni (10) in double figures.
Devon van Oostrum returned to the fold while Stanford graduate Jaiden Delaire came off the bench to make his debut.
Dimitrios Agravanis (18) and Georgios Papagiannis (14) led a team effort from Greece.