Hardware‐software co‐design systems abound in diverse modern application areas such as automobile control, telecommunications, big data processing, and cloud computing. Existing works on reliability modeling of the co‐design systems have mostly assumed that hardware and software subsystems behave independently of each other. However, these two subsystems may have significant interactions in practice. In this paper, an analytical approach based on paths and integrals is proposed to analyze reliability of nonrepairable hardware‐software co‐design systems considering interactions between hardware and software during the system performance degradation and failure process. The proposed approach is verified using the Markov‐based method. As demonstrated by case studies on systems without and with warm standby sparing, the proposed approach is applicable to arbitrary types of time‐to‐failure or degradation distributions. Effects of different transition and fault detection/recovery parameters on system performance are also investigated through examples.