Retromer is a multi-protein complex that recycles transmembrane cargo from endosomes to the trans-Golgi network and the plasma membrane. Defects in retromer impair various cellular processes and underlie some forms of Alzheimer’s disease and Parkinson’s disease. Although retromer was discovered over 15 years ago, the mechanisms for cargo recognition and recruitment to endosomes have remained elusive. Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal from the divalent cation transporter DMT1-II. This analysis identifies a binding site for canonical recycling signals at the interface between VPS26 and SNX3. In addition, the structure highlights a network of cooperative interactions among the VPS subunits, SNX3, and cargo that couple signal-recognition to membrane recruitment. Display omitted •SNX3 participates in both retromer recruitment to membranes and cargo recognition•Canonical recycling signals bind to a site at the interface between SNX3 and VPS26•Signal recognition involves a conformational change in VPS26 upon SNX3 binding•The results suggest a mechanism for assembly of retromer coats on recycling tubules Elucidation of how the full-size retromer complex recognizes a specific cargo reveals a mechanism for coupling membrane recruitment with cargo selection.