The Central Basin in the Sea of Marmara is a syntectonic basin related to the evolution of the North Anatolian fault. A well-dated (ca. 15.5–16 ka) homogenite sediment can be used as a marker in three-dimensional depth model calculations, allowing a precise determination of the seafloor subsidence rates during the Holocene. A steady-state model based on the propagation of the rates downward through the basin fill provides a good correlation with the deeper seismic reflection imagery for the past 250 ka but indicates variation of subsidence pattern for older ages. Heat flow measured at the seafloor is affected by sedimentation blanketing effects. Heat flow and subsidence data can only be reconciled if the Central Basin depocenter migrated northward with time. According to that scenario, subsidence and deposition started earlier (ca. 5–3.5 Ma) in the southern subbasin, and an acceleration of subsidence in the northern subbasin occurred at ca. 2.5–1.5 Ma. These results allow us to propose that a southern fault system distinct from the Main Marmara fault is responsible for the southern onset of the subsidence. Changes in the fault network and slip rates are implied during the last 2.5–1.5 Ma despite no apparent change since 250 ka.