The sliding of a sharp nanotip on graphene completely immersed in water is investigated by molecular dynamics (MD) and atomic force microscopy. MD simulations predict that the atomic-scale stick–slip is almost identical to that found in ultrahigh vacuum. Furthermore, they show that water plays a purely stochastic role in sliding (solid-to-solid) friction. These observations are substantiated by friction measurements on graphene grown on Cu and Ni, where, oppositely of the operation in air, lattice resolution is readily achieved. Our results promote friction force microscopy in water as a robust alternative to ultra-high-vacuum measurements.