Post-collisional volcanism contains important clues for understanding the processes that prevail in orogenic belts, including those in the mantle and the uplift and collapse of continents. Here we report new geochronological and geochemical data for a suite of post-collisional Miocene to Pleistocene volcanic rocks from northwest Iran. Four groups of volcanic rocks can be distinguished according to their geochemical and isotopic signatures, including: (1) Miocene depleted lavas with high Nd and Hf but low Pb and Sr isotopic ratios, (2) less depleted lavas with quite variable Pb isotopic composition, (3) lavas with non-radiogenic Nd and Hf isotopic values, but highly radiogenic Sr and Pb isotopic composition, and (4) Pleistocene adakitic rocks with depleted isotopic signatures. The isotopic data reveal that the Miocene rocks are derived from asthenospheric and highly heterogeneous sub-continental lithospheric mantle sources. Evidence suggests that the lithospheric mantle contains recycled upper continental material and is isotopically similar to the enriched mantle two (EMII) end-member. Analysis of Sr-Nd-Pb-Hf-O isotopes in both mineral and rock groundmass, in conjunction with energy-constrained assimilation and fractional crystallization (EC-AFC) numerical modeling, demonstrates that the incorporation of continental crust during magma fractionation via AFC had an insignificant impact on the isotopic composition of the Miocene lavas. Moreover, adakites are the youngest rocks and show a geochemical signature consistent with the partial melting of a young and mafic continental lower crust. Both seismological data and geochemical signatures on these Miocene to Pleistocene volcanic rocks indicate the initiation of asthenospheric upwelling and orogen uplift in the Arabia-Eurasia collision zone, which occurred after slab break-off, following the Neotethyan closure.