This study investigates the behavior of first-story columns under reversed cyclic lateral loading and constant axial loading by using a full-scale, one-and-a-half story subassemblage testing scheme. Four subassemblages were designed with steel beams at the second floor and a moderately ductile built-up box column with a width-thickness ratio (b/t) of either 16.2 or 20.5, which are between the highly ductile (=12.9) and moderately ductile (=23.5) requirements in AISC 341 (2016). All built-up box columns were made by SM570MB steel with a nominal yield stress, Fy= 420 MPa. A high axial load (=4200–8000 kN, corresponding to 0.2–0.4 times the axial yield strength Py) was applied to the one-and-a-half story subassemblage column before cyclic lateral drifts. The second-floor beams and column provide rotational flexibility at the top end of first-story columns in the subassemblages, significantly changing column’s stiffness, moment distribution, and inflection point location observed from typical column testing. The subassemblage column and the isolated column had a similar maximum moment at the first cycle of 0.04 rad drift, but the later showed larger strength degradation in the following cycles due to larger fixity at the column top end. An experimental solution that relates the column width-thickness ratio to the moment strength deterioration was developed to obtain design b/t limits for highly and moderately ductile built-up box columns under combined high axial load (0.3–0.4Py) and cyclic lateral drift.