While mechanical and frictional properties of graphene in air have been extensively studied, graphene’s nanomechanical behavior in liquids, vital for its operation in rechargeable batteries, super-capacitors, and sensors, is still largely unexplored. In this paper we investigate the nanomechanics of normal (adhesive and elastic) and tangential (friction) forces between a stationary, moving and ultrasonically excited nanoscale atomic force microscope (AFM) tip and exfoliated few layer graphene (FLG) on SiO2 substrate as a function of surrounding media – air, polar (water) and non-polar (dodecane) liquids. We find that while the friction coefficient is significantly reduced in liquids, and is always lower for FLG than SiO2, it is higher for graphene in non-polar dodecane than highly polar water. We also confirm that in ambient environment the water meniscus dominates high adhesion for both hydrophobic FLG and the more hydrophilic SiO2 surface, with lowest adhesion observed in liquids, in particular for FLG in dodecane, reflecting low interface energy of this system. By using nanomechanical probing via ultrasonic force microscopy (UFM) we observed profound reduction of graphene rippling and increase of graphene-substrate contact area in liquid environment. Friction force dependence on ultrasonic modulation amplitude suggests that dodecane at the graphene interface produces a solid-like “cushion” of approximately 2 nm thickness, whereas in water immersion, the same dependence shows remarkable similarity with ambient environment, confirming the presence of water meniscus in air, and suggesting negligible thickness of a similar water “cushion” on graphene. Dependence of friction on local environment opens new pathways for friction management in microfluidic, micro and nano-electromechanical systems.