We present that creating active and stable electrocatalysts remains a highly desirable and critical goal in the fields of catalysis and clean energy conversion. Single-atom catalyst (SAC), as a new research frontier in heterogeneous catalysis, has demonstrated emerging prospects for many electrocatalytic reactions. Support assisted pyrolysis approaches are widely used in the synthesis of single-atom electrocatalysts. While extensive efforts have been devoted to increase the loading of the atomically dispersed metal sites, the role of the support in creating these active metal sites remains largely unexplored. Herein, we compare catalysts created by support-free and support-assisted pyrolysis of vitamin B12 and cobalt tetramethoxyphenylporphyrin, respectively, and demonstrate an important effect of support-induced structural reconstruction that directly controls the activation of SAC. Electrochemical studies show support-free catalysts are inactive for oxygen reduction reaction whereas the support-assisted pyrolysis yields highly active catalysts using the same molecular precursors. X-ray absorption spectroscopy experiments reveal that both the metal-nitrogen coordination and the type of nitrogen species are different in these two types of samples, which leads to a difference in the d-band of the cobalt metal center and ultimately controls the catalytic activity and stability. In conclusion, this new insight provides a unique perspective on how to tune the electrocatalytic performances of SAC at the molecular level.