As a promising alternative refrigerant for meeting carbon reduction targets, R32+R1234yf binary mixtures combine the thermal performance of R32 with the environmental performance of R1234yf. Since the degree of heat dissipation during the boiling process is closely related to bubble behavior, the bubble growth and heat transfer characteristics of R32+R1234yf mixtures must be understood in depth. Accordingly, this study proposed a numerical model for single bubble growth during nucleate pool boiling of mixtures. Numerical simulations of single bubble growth in R32, R1234yf, and four binary mixtures thereof were conducted. Owing to the preferential evaporation of the more volatile component, a low concentration region of R32 appeared in the liquid near the heating surface, while the concentration of R32 in the vapor was generally higher than that in the liquid. The evaporation heat flux at the bubble interface in the mixtures was significantly lower than in pure R32, indicating that the existence of mass transfer resistance considerably reduced the heat transfer capacity of mixtures. In contrast to a pure fluid, the microlayer evaporation in a mixture might terminate owing to an increase in the local bubble point temperature, and two modes of microlayer evaporation—called “bubble-point-controlled mode” and “thickness-controlled mode”—were identified accordingly. The total heat transferred during bubble growth first decreased and then increased with an increase in the bulk concentration of R32; a minimum value was observed at an R32 mol fraction of approximately 0.4. This result is consistent with the observed variation in the difference between the vapor and liquid phase concentrations. Overall, this study provides a detailed description of the mass and heat transfer characteristics during single bubble growth in binary mixtures, contributing to a deeper understanding of the associated boiling heat transfer mechanisms.