Developing high performance electrocatalysts for the cathodic oxygen reduction reaction (ORR) is essential for the widespread application of fuel cells. Herein, a promising Pt2NiCo atomic ordered ternary intermetallic compound with N-doped carbon layer coating (o-Pt2NiCo@NC) has been synthesized via a facile method and applied in acidic ORR. The confinement effect provided by the carbon layer not only inhibits the agglomeration and sintering of intermetallic nanoparticles during high temperature process but also provides adequate protection for the nanoparticles, mitigating the aggregation, detachment and poisoning of nanoparticles during the electrochemical process. As a result, the o-Pt2NiCo@NC demonstrates a mass activity (MA) and specific activity (SA) of 0.65 A/mgPt and 1.41 mA/cmPt2 in 0.1 mol/L HClO4, respectively. In addition, after 30,000 potential cycles from 0.6 V to 1.0 V, the MA of o-Pt2NiCo@NC shows much lower decrease than the disordered Pt2NiCo alloy and Pt/C. Even cycling at high potential cycles of 1.5 V for 10,000 cycles, the MA still retains ∼70%, demonstrating superior long-term durability. Furthermore, the o-Pt2NiCo@NC also exhibits strong tolerance to CO, SOx, and POx molecules in toxicity tolerance tests. The strategy in this work provides a novel insight for the development of ORR catalysts with high catalytic activity, durability and toxicity tolerance.