Insect flight is a complex behaviour that requires the integration of multiple sensory inputs with the flight motor output. Although previous genetic studies identified central brain monoaminergic neurons that modulate Drosophila flight, neuro-modulatory circuits underlying sustained flight bouts remain unexplored. Certain classes of dopaminergic and octopaminergic neurons are known to project to the Mushroom Body, a higher integrating centre in the insect brain, where based on contextual cues they modify neuronal output and thereby organismal behaviour. This study focuses on how monoaminergic modulation of Mushroom Body GABAergic output neurons regulates the duration of flight bouts. We demonstrate that flight inactivity is maintained by activity in specific Mushroom Body GABAergic output neurons. Longer flight bouts require inhibition of these neurons by activation of central dopaminergic neurons (Protocerebral Anterior Medial or PAM), resulting in disinhibition. Moreover, octopaminergic neurons in the sub-esophageal zone stimulate PAM neurons. Because similar neurons in the sub-esophageal zone are known to respond to hunger, food search is a likely contextual cue for disinhibition in the identified neural circuit.