The Bills took advantage of five Eagles turnovers, scoring 17 points off the miscues.
Jackson gained 111 yards on the ground in 26 carries and hauled down six passes for 85 more for the Bills (4-1), who rebounded from their first loss of the year last week.
The Eagles, meanwhile, fell to 1-4 in a mistake-filled effort.
Micheal Vick was picked off four times -- one of which was returned for a 31-yard touchdown by linebacker Nick Barnett with 1:49 left.
Megyn Kelly: Santa Claus and Jesus are both white men
Twerking Brooklyn burglar 'dropped it like it was hot' prior to theft