This work elucidates friction in Poly-Ether-Ether-Ketone (PEEK) sliding contacts through multiscale simulations. At the nanoscale, non-reactive classical molecular dynamics (MD) simulations of dry and water-lubricated amorphous PEEK-PEEK interfaces are performed. During a short running-in phase, we observe structural transformations at the sliding interface that result in flattening of the initial nanotopographies accompanied by strong polymer chain alignment in the shearing direction. Our MD simulations reveal a linear pressure-dependence of the shear stress τMD (P,σH2o) [MPa]=0.18P + 50.5 - 1.25σH2o, where σH2o [nm-2] is the surface number density of adsorbed water molecules. This constitutive law is of central importance for our multiscale approach, since it forms a link between MD and elastoplastic contact mechanics calculations. An integration of τMD (P,σH2o) over the real area of contact yields a macroscopic friction coefficient μmacro (σH2o) that allows for a meaningful comparison with friction coefficients μexp≈0.5-0.7 which are in good agreement with the calculated dry friction coefficients μmacro(σH2o=0).For milder experimental loads, our multiscale model suggests that the lower friction states with μexp≈0.2 originate in the presence of physisorbed molecules (e.g. water), which significantly reduce interfacial adhesion.