The former Charlton Athletic striker headed home Dean Cox's cross after 16 minutes for his 17th goal of the season.
Leyton Orient nearly profited from a goalmouth scramble early on, but Mathieu Baudry could only poke over the bar.
Ryan Hall had a couple of decent efforts on goal, and his best chance came just after the half-hour mark when his strike was saved by Jamie Jones.
The Dons went close towards the end of the half but Izale McLeod's cross couldn't be met by Hall before Jordan Spence drilled wide.
With the half petering out, Lisbie popped up with a cool finish to put his side in a commanding position at the break.