The Middle East region represents a key site within the Tethyan domain where continental break-up, collision, backarc extension and escape tectonics are kinematically linked together. We perform global mantle circulation computations to test the role of slab pull and mantle upwellings as driving forces for the kinematics of the Arabia-Anatolia-Aegean (AAA) system, evaluating different boundary conditions and mantle density distributions as inferred from seismic tomography or slab models. Model results are compared with geodetically inferred crustal motions, residual topography, and shear wave splitting measurements. The AAA velocity field with respect to Eurasia shows an anti-clockwise toroidal pattern, with increasing velocities toward the Aegean trench. The best match to these crustal motions can be obtained by combining the effect of slab pull exerted in the Aegean with a mantle upwelling underneath Afar and, more generally, with the large-scale flow associated with a whole mantle, Tethyan convection cell. Neogene volcanism for AAA is widespread, not only in the extensional or subduction settings, but also within plates, such as in Syria-Jordan-Israel and in Turkey, with geochemical fingerprints similar of those of the Afar lava. In addition, morphological features show large uplifting domains far from plate boundaries. We speculate that the tectonic evolution of AAA is related to the progressive northward entrainment of upwelling mantle material, which is itself associated with the establishment of the downwelling part of a convection cell through the segmented Tethyan slab below the northern Zagros and Bitlis collision zone. The recently established westward flow dragged Anatolia and pushed the Aegean slab south-westward, thus accelerating backarc extension. Our model reconciles Afar plume volcanism, the collision in the Bitlis mountains and northern Zagros, and the rapid increase of Aegean trench rollback in a single coherent frame of large scale mantle convection, initiated during the last similar to 40 Ma. (C) 2013 Elsevier B.V. All rights reserved.