A surgical instrument includes an elongated shaft having a proximal structural member and a proximal drive member that is selectively movable with respect to the proximal structural member. A modular end effector is removably coupled to the elongated shaft, and has a distal structural member and a distal drive member that is operatively coupled to a pair of jaw members. A separable joint is defined between the elongated shaft and the end effector. The separable joint includes laterally prominent and laterally indented portions of each of the proximal and distal structural members and of each of the proximal and distal drive members. The structural members are interlocked to resist longitudinal separation and permit lateral separation. The drive members are movable relative to structural members to move the separable joint to a locked configuration wherein the drive members prohibit lateral separation of the structural members.