U's goalkeeper Ben Williams turned away Peter Hartley's header, but both debutant Kayode Odejayi and fellow forward Clive Platt went close with headers for Colchester and John-Joe O'Toole's long-range effort whistled inches wide.
Lisbie squandered the chance to put the U's in front six minutes before the break when he blasted a penalty over after Sam Collins had shoved Odejayi in the area.
But he made amends five minutes later when he confidently slotted home from the spot after Gary Liddle had wrestled Odejayi down in the area.
Colchester got the chance to extend their lead 30 seconds into the second half. Liddle was adjudged to have handled John White's long throw into the box and Lisbie converted his second penalty of the game and his sixth goal of the season. Odejayi was denied by Scott Flinders as Colchester ran out comfortable winners.