Abstract: Metal–fluorine (MF) diatomic molecules, such as YbF and PbF, are extensively utilized in precision spectroscopy and fundamental physics applications. For instance, they are suitable candidates for the search of electric dipole moments (EDMs) and the investigation of laser cooling systems. Studying how to generate these molecules effectively and productively is of significant importance. In the present work, we focus on the generation of YbF and PbF through chemical reactions involving Yb, Pb atoms ablated from an Yb-, Pb-metal targets and two most commonly used fluorine-containing gases, SF₆ and CF₄. The reactions are investigated theoretically using density functional theory (DFT) and experimentally employing the laser-ablation/laser-induced fluorescence (LIF) technique to compare the efficiencies of YbF and PbF molecule generation. Computational results suggest that when generating PbF, the use of SF₆ as the fluorine gas enhances the yield in comparison to CF₄, which is consistent with our experimental results. On the contrary, for YbF, while theoretical calculations similarly advocate for SF₆ yielding higher yields, the experimental results contradict this conclusion. Furthermore, theoretical predictions propose that metal atoms in an excited state can promote the progress of the reaction.