Autophagy is a constitutive process of lysosomal degradation required for maintaining the homeostasis of large molecular complexes and organelles in neurons. Here we reported a systemic investigation of neuronal autophagy targets through integrated proteomics and functional analysis. Proteomic profiling of human and mouse neurons with autophagy inhibition and LC3-interactome reveals a role for neuronal autophagy in targeting a wide range of cellular pathways and organelles. Our study reveals the landscape of autophagy degradation in neurons and insight into mechanisms of neurological disorders linked to autophagy deficiency.