Current research efforts on single-atom catalysts (SACs) exclusively focus on nonmetal or transition-metal atoms as active centers, while employing main-group metal elements is seemingly excluded because their delocalized s/p-bands are prone to yield a broadened resonance for the interaction with adsorbates. Here, we use high-throughput first-principles calculations to investigate the possible incorporation of Mg, Al, and Ga to form graphene-based SACs for NO reduction reaction (NORR) toward NH₃. 51 SAC candidates with different metal coordination environments have been computationally screened employing a rationally designed four-step process, yielding six SACs with high catalytic activity and NORR selectivity. The performance is rationalized by the modulation of s/p-band filling of the main-group metals. The adsorption free energy of NO is identified as an efficient descriptor for such SACs. The underlying physical mechanism is revealed and generally applicable to other main group metal SACs. These fundamental insights extend NORR SACs to main-group metal elements.