Catalyst stability in the liquid phase under polar conditions, typically required for the catalytic conversion of renewable platform molecules, is a major concern but has been only sparsely studied. Here, the activity, selectivity, and stability of Ru-based catalysts supported on TiO2, ZrO2, and C in the conversion of levulinic acid (LA) to γ-valerolactone (GVL) has been studied at 30 bar of H2 and 423 K in dioxane as solvent. All catalysts showed excellent yields of GVL when used fresh, but only the Ru/ZrO2 catalyst could maintain these high yields upon multiple recycling. Surprisingly, the widely used Ru/TiO2 catalyst showed quick signs of deactivation already after the first catalytic test. XPS, CO/FT-IR, TGA, AC-STEM, and physisorption data showed that the partial deactivation is not due to Ru sintering or coking but rather due to reduction of the titania support in combination with partial coverage of the Ru nanoparticles, i.e. due to a detrimental strong metal–support interaction. In contrast, the zirconia support showed no signs of reduction and displayed high morphological and structural stability even after five recycling tests. Remarkably, in the fresh Ru/ZrO2 catalyst, Ru was found to be fully atomically dispersed on the fresh catalyst even at 1 wt % Ru loading, with some genesis of Ru nanoparticles being observed upon recycling. Further studies with the Ru/ZrO2 catalyst showed that dioxane can be readily replaced by more benign solvents, including GVL itself. The addition of water to the reaction mixture was furthermore shown to promote the selective hydrogenation reaction.