To develop lightweight, high-strength and environmentally friendly prefabricated panels, this paper proposed a novel GFRP plate-sheathed cold-formed steel (CFS) composite panel (GFRP-CFS panel) filled with lightweight phosphogypsum (LPG) and investigated its flexural performance experimentally, numerically and theoretically. Firstly, nine full-scale specimens were subjected to four-point bending test. The effects of the number, web height, thickness and arrangement of the longitudinal CFS studs, the number of lateral CFS studs, and the support connection on the flexural performance were discussed. Results indicate that the failure mode of the GFRP-CFS panels was debonding of GFRP plate in the compression zone at midspan and local buckling of CFS below the loading point. The strain of GFRP plate always lagged behind that of the CFS stud at the corresponding position, and the built-up cross section of the panel no longer conformed to the plane-section assumption. In addition, a nonlinear finite element modelling (FEM) analysis based on DIANA software was conducted to validate the test results. The load-deflection response, strain response and failure mode from the FEM analyses were in good agreement with the test results. Furthermore, based on the theoretical analysis considering the bond-slip effect between GFRP and CFS, a closed-form solution for the GFRP utilization coefficient was derived. The effect of different variables on the GFRP utilization coefficient was analyzed through parametric analysis. Finally, the calculation method for the flexural strength and ultimate deflection of GFRP-CFS panels were established, and the predicted results were in good agreement with test results. Therefore, the developed GFRP-CFS panels have excellent potential for prefabricated floor and wall applications.