The temporal variation in the size of Ontario Lacus, the largest lake in the southern polar region of Titan, over the past 45 kyr caused by seasonal and orbital forcing is simulated by a lake balance model along with the meteorological input from paleoclimate simulations. Orbital forcing can change the lake volume and lake area by a factor of up to three to four, mainly due to a long-term variation in precipitation rate. If fast infiltration at the lakebed is assumed to take place, seasonal and secular variation in lake size have similar magnitudes, resulting in a perpetual cycle of drying and flooding of shallow portions of the lake with a period of 30 years. If instead Ontario Lacus is a terminal lake without infiltration, the lake size varies little with season but undergoes larger secular variations. In this case the lake size is strongly out of equilibrium with the instantaneous methane budget of the lake. Orbitally forced flooding of the plain southeast of Ontario Lacus could explain the presence of evaporites. On the other hand, orbital forcing alone cannot cause Ontario Lacus to become as large as the observed possible paleosea since the precipitation in the catchment area does not change by orders of magnitude. Likewise, Ontario Lacus is unlikely to have entirely desiccated over the past 45 kyr.