This paper presents an experimental study of the seismic performance of high-strength concrete-filled box columns (CFBCs) under combined axial and cyclic lateral loads. Specimens were made of high-strength SM 570 M steel (with yield strengths between 520 and 580 MPa), and concrete with compressive strength (f(c)) greater than 80 MPa. Three parameters that affect the seismic performance of CFBCs were investigated: the width-to-thickness (b/t) ratio of the steel column, magnitude of the axial load, and the addition of concrete infill. The specimens, which were 280-420 mm in width and 2000 mm in height, were tested under combined axial (4058-10,090 kN) and cyclic lateral loads. Experimental results indicated that the lateral displacement ductility decreases significantly with an increase in either the axial load or b/t ratio. The addition of concrete infill inside a hollow steel box column does not improve the lateral displacement ductility of CFBCs under high axial load. Although the CFBC specimens satisfied the b/t requirement of a highly ductile member, as per AISC Seismic Provisions (2016), specimens under high axial load (40%P-n) failed at 4% drift, indicating that the requirement does not guarantee that CFBCs will sustain high axial load under significant drift (i.e., > 3%). The Eurocode 4 (2009), AISC Specification (2010), and Architectural Institute of Japan (2014) reasonably estimate the flexural strength of high-strength CFBCs under axial load; however, ACI 318 (2011) does not. The finite element analysis program ABAQUS can be used to estimate the hysteretic behavior of specimens before significant strength degradation.