The three points ensures the O's finish the regular League One season in third, meaning the second leg of that tie is at their Brisbane Road home, while the Dons' season finished with a whimper
Orient took the lead after 17 minutes when Dean Cox sent in a terrific cross from the left and Lisbie comfortably headed in at the back post.
Lisbie then claimed his second right on half-time and again Cox was the provider, this time threading a lovely through-ball with Lisbie finishing coolly into the bottom corner.
The O's put the result beyond doubt when Lisbie's pass slid in David Mooney and he smashed in his 21st goal of the season with a brilliant strike into the top corner from a narrow angle.
Dons scored a consolation with 12 minutes left as Ryan Hall's shot from the edge of the area was deflected in.