The analysis of masonry-infilled frames (MIFs) with openings is a complex problem in structural engineering. Previous studies have shown that when an infill panel has an opening, it behaves as four separate subpanels around the opening. Therefore, it can be conceived that a perforated masonry infill panel behaves as four inclined compression-only equivalent struts in each direction. This paper presents a multi-strut model (MSM) using the equivalent strut concept for the nonlinear analysis of masonry-infilled steel frames (MISFs) with openings. The MSM consists of two inelastic side pier struts connected to the surrounding frame joints using rigid trusses representing the subpanels above and below the opening. The model incorporates an envelope curve and a hysteretic law to define the initial stiffness, peak strength, and post-peak strength behavior of the inclined struts under reversal loads. The MSM was used to analyze the lateral load behavior of tested MISFs with openings found in the literature. It was shown that the proposed model is efficient and can predict the stiffness and capacity of MISFs with openings under both monotonic and cyclic lateral loadings.