Porphyry Cu fertility of magmatic arcs is normally heterogeneous in space and time, which may have controlled the spatiotemporal distribution of both syn- and post-subduction porphyry Cu deposits. However, it remains unclear whether such heterogeneity applies to the Paleo-Tethyan arc belt that was previously conjectured to be infertile due to anoxia in its ocean basin and reduced derivative arc magmas. The eastern Tibetan Plateau encompasses two Paleo-Tethyan arc segments (i.e. Zaduo and Jiangda), with the latter endowed with intensive post-subduction porphyry–skarn Cu mineralization. This offers a unique opportunity to fully assess the Paleo-Tethyan arc magma fertility and to unveil its genetic linkage with spatially associated post-subduction porphyry Cu deposits. A synthesis of new and published data indicates highly heterogeneous porphyry Cu fertility for both segments, which differs significantly with previous views. Specifically, the middle Permian arc rocks (275–260 Ma) are reduced and S-deficient, indicating low Cu fertility. In contrast, the late Permian (260–250 Ma) arc rocks have elevated though scattered whole-rock Fe3+/Fe2+, zircon EuN/EuN* and ΔFMQ values, and zircon copper fertility index (ZCFI, a composite fertility index calculated from zircon composition) values, as well as apatite and estimated melt S contents. The upper limits of these parameters overlap those of global porphyry Cu ore-forming magmas and suggest high magma fertility. The increasing fertility may be caused by intracrustal processes such as crustal thickening and enhanced magma evolution, supported by the positively correlated zircon ΔFMQ values, apatite S contents, and corresponding whole-rock (La/Yb)N ratios. We further demonstrate that the two arc segments are characterized by contrasting tectonic stresses, which probably exerted an important control on the distribution of subsequent, younger post-subduction porphyry Cu deposits. Arc rocks from the Jiangda segment appear to have experienced earlier FeO depletion and sulfide saturation than those from the Zaduo segment, as expressed by lower Fe2O3T and Pd contents at given MgO values. Whole-rock (La/Yb)N ratios increase steeply with magma evolution and crystallization ages at Jiangda, but weakly at Zaduo. These differences likely indicate stronger compression in the Jiangda segment, which may have resulted in stronger crustal thickening and Cu accumulation in the arc root during the Middle to Late Permian. Remobilization of the accumulated Cu by later magmas may have formed post-subduction porphyry–skarn Cu deposits spatially associated with the Jiangda segment. Our study demonstrates highly heterogeneous porphyry Cu fertility of the Paleo-Tethyan arc belt, and shows that the compressive tectonic stress of an arc segment may have been the key factor linking arc magmatism and post-subduction porphyry Cu deposits.