Finding an active and durable catalyst for the acidic oxygen reduction reaction (ORR), a key process for fuel cells, remains an open challenge due to the thermodynamically contradictory requirements for activity and durability. Here, we report that an active and durable ORR catalyst can be achieved by integrating multiple structural and compositional advantages into one catalyst. The mass activity and specific activity of as-obtained 1-nm-thick PtNiRh trimetallic nanowires/C catalyst were 15.2 and 9.7 times as high as that of commercial Pt/C catalyst, respectively. The compressive strain and ligand effects arising from the advantageous microstructure and optimal composition of the nanowires were revealed to enhance the activity. Besides, the PtNiRh trimetallic nanowires/C catalyst exhibited substantially improved durability relative to commercial Pt/C catalyst, due to the combination of its one-dimensional structure and incorporated Rh atoms. This work provides a general guidance for the design of an impressive heterogeneous catalyst.