A composite large-span open-web floor (COF) system is introduced in this paper, which is composed of I-shaped steel chords, steel tube webs, and concrete slabs. One COF specimen was fabricated and tested under cyclic loadings. The failure process and hysteretic curve of the specimen were discussed in detail. Moreover, a finite element (FE) model was developed and verified by experimental results. A parametric study was performed to examine the effects of the concrete strength, steel strength, section steel thickness, and structural height. The parametric study demonstrates that the effects of the steel strength, section steel thickness, and structural height on the load-displacement hysteretic curve are proved to be significant. As for the bearing capacity and stiffness degradation of the COF system, the influence of the steel strength and section steel thickness is stronger than that of the concrete strength and structural height. Additionally, it is also found that the influence of the steel strength and section steel thickness on the energy dissipation is remarkable; the energy dissipation ability of the structure decreased with increasing the steel strength and increased with increasing the thickness of section steels.