Closed-form structural stress solutions are investigated for fatigue life estimations of flow drill screw (FDS) joints in lap-shear specimens of aluminum 6082-T6 sheets with and without clearance hole based on three-dimensional finite element analyses. The closed-form structural stress solutions for rigid inclusions under counter bending, central bending, in-plane shear and in-plane tension are first presented. Three-dimensional finite element analyses of the lap-shear specimens with FDS joints without and with gap (with and without clearance hole) are then presented. The results of the finite element analyses indicate that the closed-form structural stress solutions are quite accurate at the critical locations near the FDS joints in lap-shear specimens without and with gap (with and without clearance hole) for fatigue life predictions. The fatigue life predictions based on the closed-form and computational structural stress solutions are in agreement with the experimental results for FDS joints in lap-shear specimens without and with gap (with and without clearance hole) under high-cycle fatigue loading conditions.