Cold-formed light gauge steel framing (LSF) structure is a new type of fabricated steel structure. Fire resisting performance of LSF structure is the key factor for promoting related practical application. However, for the LSF floor as one of the main load–bearing systems in LSF structures, the available fire testing data are limited. Most of the published numerical investigations of LSF floors are carried out by using two-dimensional heat transfer analysis to study the temperature rise and distribution, or simplified linear temperature distributions. The difference between the analysis results of two-dimension and three-dimension structural members could accumulate and evolve into the essential discrepancy in force transfer when the structural scale is large and the system is complex. To determine the mechanism of the fire resistance, the model describing a floor system consists of LSF, structural plywood, and fire-resistant panel such as gypsum board or rock wool was built up in this article. According to the ISO-834 standard, the nonlinear heat process and coupled thermo-mechanical analyses were carried out. Hence, the influence of the three-dimensional thermal field and the coupling mechanical behaviors were demonstrated. In addition, a simplified modeling approach was presented to accurately describe the contact relationship, force transfer, and the deformation coordination between self-tapping screws, structural plates, and light steel members. After comparing with two sets of fire testing data for the full-scale floor slab systems, the mechanism drawn from the numerical simulation above mentioned was verified. In general, this model based on three-dimensional heat conduction and thermal-mechanical coupling can effectively describe the LSF spatial mechanical behavior under fire conditions. The results about nonlinear temperature distribution, the deformation evolution of the joists, and the final destruction mode are consistent with those of fire testing. The proposed modeling strategy can be utilized to predict the fire resistance of LSF floor systems and evaluate the effective factors on structural high-temperature behaviors via parametric analysis.