The Apt Basin, sub-basin of the wider Manosque Basin of southeastern France, hosts deposits of Eocene-Oligocene lake systems that were part of a wider network of evaporative lakes and lagoons spread over the European Cenozoic rift system. The onset and mechanisms of subsidence in the rift system, the inter-connectivity of these lakes, and their response to the fall into the Oligocene icehouse are poorly understood. This study aims at documenting these points by clarifying the stratigraphy and depositional environments in the Apt Basin. We correlate and date Eocene-lowermost Oligocene geological units using a basin-wide facies model and a combination of sedimentological and geochronological approaches. We show the existence of three lacustrine phases separated by complete lake drying events: (1) an Ypresian (?) - Lutetian lake-marsh system dominated by palustrine carbonates; (2) a Bartonian (?) - Priabonian siliciclastic fluvio-deltaic & saline lake system; and (3) a lower Rupelian saline carbonate lake system. The existence of a first lake system during the Ypresian (?) - Lutetian indicates an onset of basin subsidence before most other basins of the rift system in southeastern France, and is associated with the late Pyrenean deformation phase. The initiation of the second lacustrine phase marks the onset of E-W extension and the formation of the Apt Basin as an individual horst & graben system. Based on facies distribution, we show the hydrological isolation of the Apt Basin from other basins and the unlikeliness of any connection with the sea during the first two phases. This isolation is less clear for the third phase. We show a close synchronicity of the second lake drying event with the Eocene-Oligocene Transition. The third lacustrine phase, dominated by carbonate production and low siliciclastic input, is interpreted as reflecting a long-lasting decrease in surface run-off associated with the fall into the Oligocene icehouse.