Endocellulases are central to cellulose deconstruction but are commonly viewed as stochastic catalysts whose product distributions are difficult to control. Here, we report a loop encoded mechanism that governs cleavage-site selection in GH5 endocellulases. By comparing two closely related enzymes with distinct product profiles, we show that a short loop near the binding cleft determines substrate positioning and hydrolytic outcomes. Molecular dynamics simulations reveal that a triaspartate loop