The friction of a solid contact typically shows a positive dependence on normal load according to classic friction laws. A few exceptions were recently observed for nanoscale single-asperity contacts. Here, we report the experimental observation of negative friction coefficient in microscale monocrystalline heterojunctions at different temperatures. The results for the interface between graphite and muscovite mica heterojunction demonstrate a robust negative friction coefficient both in loading and unloading processes. Molecular dynamics simulations reveal that the underlying mechanism is a synergetic and nontrivial redistribution of water molecules at the interface, leading to larger density and more ordered structure of the confined subnanometer-thick water film. Our results are expected to be applicable to other hydrophilic van der Waals heterojunctions.