Experimental and numerical studies were conducted to investigate the in-plane behavior of the steel–concrete composite frame slab under cyclic loads. In the experimental study, an in-plane loading test of a typical composite frame slab was designed by constraining its out-of-plane deformations. The test observations, the load–displacement relationship, and the shear and flexural deformation components were discussed to investigate the in-plane load resistant behavior and the failure mechanism of the slab. The experimental results demonstrated an evident shear cracking concentration behavior and a pinching hysteretic curve associated with a typical shear-tension failure mode of the composite frame slab. In the numerical study, a high-efficiency modeling scheme based on the multiple vertical line element model (MVLEM) and the fiber beam–column element was developed for the test specimen. Comparisons with the experimental results showed that the developed model predicted the overall load–displacement relationship, the relationships associated with the shear and flexural deformation components, and the failure mode with a reasonable level of accuracy.