Elucidating the correlation of the polymer precursors and active sites formation of multi-heteroatom doped based carbon for oxygen reduction reaction (ORR) is essential to develop molecular-level design of highly efficient metal-free carbon catalysts. To achieve this goal, herein, two series of N doped and N, S co-doped carbon nanospheres were synthesized via pyrolysis of self-polymerized compounds of three analogous precursors of 2,6-Diaminopyridine, 4, 6-Diaminopyrimidine and 1,3-Diaminobenzene as nitrogen source initiated by hydrogen peroxide and ammonium persulfate as sulfer source respectively. The results demonstrate that nitrogen atoms in the six-membered rings of three precursors play a critical role on the formation of N-doping types and synergistic effects of N and S dopants in their derived carbon nanoshperes for ORR. Among the three precursors, 2,6-Diaminopyrimidine prefers to form the Pyridinic N doped carbon, resulting in the highest activity for ORR in N doped nanospheres, in contrast, 2,6-Diaminopyridine facilitates the formation of more content of Graphitic-N dopant, which has stronger synergy with thiophenic-S dopant in carbon matrix than that of Pyridinic N dopants. This unique characteristic endows 2,6-Diaminopyrimidine derived N, S co-doped nanospheres with excellent ORR activity of higher half-wave potential of 0.87 V vs. RHE in 0.1 M KOH and Zn-Air battery power output performance than that of the same loading of commercial Pt/C catalyst. Revealing the dependence of specific active sites determined by precursors with very similar molecular structures in the work will shed light on the precise design strategy based on the precursors-selecting guidance for the development of advanced multi-heteroatom doped carbon ORR catalysts. (C) 2020 Elsevier Inc. All rights reserved.