Formic acid oxidation (FAO) is a typical anode reaction in fuel cells that can be facilitated by modulating its direct and indirect reaction pathways. Herein, PtAu bimetallic nanoparticles loaded onto Co and N co-doping carbon nanoframes (CoNC NFs) were designed to improve the selectivity of the direct reaction pathway for efficient FAO. Based on these subtle nanomaterials, the influences of elemental composition and carbon-support materials on the two pathways of FAO were investigated in detail. The results of fuel cell tests verified that the appropriate amount of Au in PtAu/CoNC can promote a direct reaction pathway for FAO, which is crucial for enhancing the oxidation efficiency of formic acid. In particular, the obtained PtAu/CoNC with an optimal Pt/Au atomic ratio of 1:1 (PtAu/CoNC-3) manifests the best catalytic performance among the analogous obtained Pt-based electrocatalysts. The FAO mass activity of the PtAu/CoNC-3 sample reached 0.88 A·mg_Pt⁻¹, which is 26.0 times higher than that of Pt/C. The results of first-principles calculation and CO stripping jointly demonstrate that the CO adsorption of PtAu/CoNC is considerably lower than that of Pt/CoNC and PtAu/C, which indicates that the synergistic effect of Pt, Au, and CoNC NFs is critical for the resistance of Pt to CO poisoning. This work is of great significance for a deeper understanding of the oxidation mechanism of formic acid and provides a feasible and promising strategy for enhancing the catalytic performance of the catalyst by improving the direct reaction pathway for FAO.