It is agreed that mantle dynamics have played a role in generating and maintaining the elevated topography of Anatolia during Neogene times. However, there is debate about the relative importance of subduction zone and asthenospheric processes. Key issues concern onset and cause of regional uplift, thickness of the lithospheric plate, and the presence/absence of temperature and/or compositional anomalies within the convecting mantle. Here, we tackle these interlinked issues by analyzing and modeling two disparate suites of observations. First, a drainage inventory of 1,844 longitudinal river profiles is assembled. This database is inverted to calculate the variation of Neogene regional uplift through time and space by minimizing the misfit between observed and calculated river profiles subject to independent calibration. Our results suggest that regional uplift commenced at 20 Ma in the east and propagated westward. Second, we have assembled a database of geochemical analyses of basaltic rocks. Two different approaches have been used to quantitatively model this database with a view to determining the depth and degree of asthenospheric melting across Anatolia. Our results suggest that melting occurs at depths as shallow as 60 km in the presence of mantle potential temperatures as high as 1400°C. There is evidence that temperatures are higher in the east, consistent with the pattern of subplate shear wave velocity anomalies. Our combined results are consistent with isostatic and admittance analyses and suggest that elevated asthenospheric temperatures beneath thinned Anatolian lithosphere have played a first‐order role in generating and maintaining regional dynamic topography and basaltic magmatism.