Autophagy is a conserved catabolic process that plays a housekeeping role in eliminating protein aggregates and organelles and is activated during nutrient deprivation to generate metabolites and energy. Autophagy plays a significant role in tumorigenesis, although opposing context-dependent functions of autophagy in cancer have complicated efforts to target autophagy for therapeutic purposes. We demonstrate that autophagy inhibition reduces tumor cell migration and invasion in vitro and attenuates metastasis in vivo. Numerous abnormally large focal adhesions (FAs) accumulate in autophagy-deficient tumor cells, reflecting a role for autophagy in FA disassembly through targeted degradation of paxillin. We demonstrate that paxillin interacts with processed LC3 through a conserved LIR motif in the amino-terminal end of paxillin and that this interaction is regulated by oncogenic SRC activity. Together, these data establish a function for autophagy in FA turnover, tumor cell motility, and metastasis. Display omitted •Autophagy is required for the migration and invasion of metastatic tumor cells•Autophagy promotes the degradation of paxillin and focal adhesion turnover•Paxillin interacts with LC3B through a conserved LIR in a Src-regulated manner•Autophagy is required for Src-regulated tumor cell motility Sharifi et al. describe a role for autophagy in focal adhesion turnover and cell motility mediated by the interaction of processed LC3 with paxillin in a manner regulated by oncogenic Src. These studies suggest potential therapeutic value in targeting autophagy to inhibit metastatic dissemination.