Aiming at the connection reliability problem of precast steel pipe-concrete composite columns, a post-stressed strengthened core-pipe connection is proposed. The columns are connected by Q420 high-strength core pipes, and anchored into the pre-embedded steel pipe of the column. The connection is strengthened by the post-tensioned unbonded tendons through the overall height of the structure. To investigate the seismic performance of the precast composite column, a low-cycled horizontal load test was carried out on a cast-in-place comparison specimen and three precast specimens with different core pipes. The seismic performance of each specimen was comprehensively evaluated by comparing the failure mode, hysteretic curve, skeleton curve, bearing capacity, stiffness, displacement ductility, and energy dissipation. Based on the test results, finite element parameter analysis of core pipe diameter and thickness, core pipe length, connecting cover plate thickness, and prestressed stress was carried out. The test and parameter analysis results show that, precast specimens can generally achieve equivalent cast-in-place seismic performance, but the adverse effects of increased structural seismic force due to increased stiffness should be considered. With the increase of the cross-sectional specification of the core pipe, bearing capacity, stiffness, and ductility of the column gradually increase, and the precast specimen with D152 mm×16 mm core pipe is recommended. Cross-section with a larger moment of inertia and equivalent area is proposed for core pipes. The bonding length of core pipes can be designed as 3 times the diameter. The thickness of the connecting cover plate can be determined by configuration. For the tested specimens, the prestressed stress is recommended to be determined within the range of 0.3fpyk~0.6fpyk.