Parallel manipulators with two rotations and one translation have been attracted the interest from both academic and industry. They can be selected as parallel modules and used in the workpieces machining. A systemic stiffness modeling and performance analysis of a 2-UPR-PRU three degrees of freedom parallel manipulator was presented based on the screw theory and strain energy, where U, P and R denoted universal, prismatic and revolute joint, respectively. Firstly, the inverse kinematics of the 2-UPR-PRU parallel manipulator was presented by using the closed-loop method. Next, considering the compliances of limbs, the stiffness matrices of limbs in the 2-UPR-PRU parallel manipulator were derived through the screw theory and strain energy, and the overall stiffness matrix of the parallel manipulator was obtained by combining the deformation compatibility equations. Under the external wrench, the deformations and overall compliance matrix of the 2-UPR-PRU parallel manipulator in different configurations were obtained, and a numerical simulation based on the ANSYS software was used to verify the correctness of the theoretical result. Finally, the distributions of virtual-work stiffness index were used to evaluate and discuss the stiffness performances of the 2-UPR-PRU parallel manipulator in different external wrenches and operational heights. The stiffness modeling and performance analysis of the 2-UPR-PRU parallel manipulator can provide an important reference for the design of prototype and the high precise control of system.