The use of cold-formed steel (CFS) built-up sections in engineering practice is widely gaining popularity due to their ability to provide sustainable solutions and optimised section design opportunities. This paper presents an experimental and numerical investigation conducted on CFS built-up stiffened box section columns under axial compression. A total of 13 new experimental tests were conducted with specimens having an overall web depth up to 550 mm. Detailed nonlinear elasto-plastic finite element (FE) models were then developed and verified against the test results. Upon verification, a parametric study involving 144 FE models was carried out to investigate the effects of section thickness, column length, and screw spacing on the buckling resistance of CFS built-up stiffened box sections. The test and finite element analysis (FEA) results were compared with the buckling resistances determined by the American Iron and Steel Institute (AISI S100) and Australian and New Zealand Standards (AS/NZS 4600). It was found that the buckling resistances determined by the AISI S100 and AS/NZS 4600 for CFS built-up stiffened box sections were conservative by 9.3% on average, compared to experimental and FEA results. Modified Direct Strength Method (DSM) design equations for predicting the buckling resistances of CFS built-up stiffened box sections were then proposed, and a reliability analysis was conducted to assess the feasibility of the proposed equations.