γ-Valerolactone (GVL) is readily obtained by the hydrogenation of levulinic acid (LA) and is considered a sustainable platform chemical for the production of biobased chemicals. Herein, the performance and stability of Ru-based catalysts (1 wt % Ru) supported on TiO2 (P25) and ZrO2 (monoclinic) for LA hydrogenation to GVL is investigated in the liquid phase in batch and continuous-flow reactors using water and dioxane as solvents. Particular attention is paid to the influence of possible impurities in the LA feed on catalyst performance for LA hydrogenation. Benchmark continuous-flow experiments at extended times on-stream showed that the deactivation profiles are distinctly different for both solvents. In dioxane, the Ru/ZrO2 catalyst is clearly more stable than Ru/TiO2, whereas the latter is slightly more stable in water. Detailed characterization studies on spent catalysts after long run times showed that the deactivation of Ru/TiO2 is strongly linked to the reduction of a significant amount of Ti4+ species of the support to Ti3+ and a decrease in the specific surface area of the support in comparison to the fresh catalyst. Ru/ZrO2 showed no signs of support reduction and displayed morphological and structural stability; however, some deposition of carbonaceous material is observed. Impurities in the LA feed such as HCOOH, H2SO4, furfural (FFR), 5-hydroxymethylfurfural (HMF), humins, and sulfur-containing amino acids impacted the catalyst performance differently. The results reveal a rapid yet reversible loss of activity for both catalysts upon HCOOH addition to LA, attributed to its preferential adsorption on Ru sites and possible CO poisoning. A more gradual drop in activity is found when cofeeding HMF, FFR, and humins for both solvents. The presence of H2SO4, cysteine, and methionine all resulted in the irreversible deactivation of the Ru catalysts. The results obtained provide new insights into the (ir)reversible (in)sensitivity of Ru-based hydrogenation catalysts to potential impurities in LA feeds, which is essential knowledge for next-generation catalyst development.