The synthesis of high-quality ultrathin overlayers is critically dependent on the surface structure of substrates, especially involving the overlayer–substrate interaction. By using in situ surface measurements, we demonstrate that the overlayer–substrate interaction can be tuned by doping near-surface Ar nanobubbles. The interfacial coupling strength significantly decreases with near-surface Ar nanobubbles, accompanying by an “anisotropic to isotropic” growth transformation. On the substrate containing near-surface Ar, the growth front crosses entire surface atomic steps in both uphill and downhill directions with no difference, and thus, the morphology of the two-dimensional (2D) overlayer exhibits a round-shape. Especially, the round-shaped 2D overlayers coalesce seamlessly with a growth acceleration in the approaching direction, which is barely observed in the synthesis of 2D materials. This can be attributed to the immigration lifetime and diffusion rate of growth species, which depends on the overlayer–substrate interaction and the surface catalysis. Furthermore, the “round to hexagon” morphological transition is achieved by etching-regrowth, revealing the inherent growth kinetics under quasi-freestanding conditions. These findings provide a novel promising way to modulate the growth, coalescence, and etching dynamics of 2D materials on solid surfaces by adjusting the strength of overlayer–substrate interaction, which contributes to optimization of large-scale production of 2D material crystals.