Hysteretic friction behavior has been observed on varied 2D nanofilms. However, no unanimous conclusion has yet been drawn on to the exact mechanism or relative contribution of each mechanism to the observed behavior. Here we report on hysteretic friction behavior of supported atomically thin nanofilms studied using atomic force microscopy (AFM) experiments and molecular dynamics (MD) simulations. Load dependent friction measurements were conducted on unheated and heated samples of graphene, h-BN, and MoS2 supported by silica substrates. Two diverging friction trends are reported: the unheated samples showed higher friction during unloading than during loading, and the heated samples showed a reversed hysteresis. Further, the friction force increased sub-linearly with normal force for heated samples, compared with unheated samples. Tapping mode AFM suggested that the interaction strength of the substrate was increased with heating. Roughened substrates in the MD simulations that mimicked strong/weak interaction forces reproduced the experimental observations and revealed that the evolution of real contact area in different interface interaction situation caused the diverging behaviors. Surface roughness and interaction strength were found to be the key parameters for controlling the out-of-plane deformation of atomically thin nanofilms.