The identification and development of novel non-noble metals based electro-catalyst exhibiting excellent electrochemical activity and stability than noble metal electro-catalyst is important for commercial development of proton exchange membrane fuel cells (PEMFCs). Such non-noble electro-catalyst with unique electronic structure and superior electrochemical performance will immensely contribute to lowering the capital cost of PEMFCs. Herein, we have identified solid solution electro-catalysts of WO3 and IrO2 for oxygen reduction reaction (ORR) in PEMFCs exploiting theoretical first principles approaches. The theoretical results were experimentally validated by generation of nano structured (W1-xIrx)O-y (x = 0.2, 0.3; y = 2.7-2.8) electro-catalysts for ORR. (W0.7Ir0.3)O-y demonstrated similar to 43% improved electrochemical activity than Pt/C with similar loading at 0.9 V (vs RHE), respectively. Moreover, single full cell PEMFC study revealed an acceptable similar to 81% improved maximum power density for (W0.7Ir0.3)O-y than Pt/C combined with excellent long term stability. These results thus, show the potential of (W0.7Ir0.3)O-y as ORR electro-catalyst for replacing of Pt/C in PEMFCs and direct methanol fuel cells on the additional grounds of superior methanol tolerance. (C) 2017 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.