Most factory production processes are completed by machines and workers on production lines. The operation schedule is arranged to reduce the cost of the enterprises to obtain the maximum economic profit for sustainable running. Previous studies usually investigated the working time while only considering the workers’ conditions. This study proposed a method to optimize the operation schedule by jointly considering the workers’ fatigue states and the operation states of machines. This method was proposed based on a system structure called the multistate consecutively connected system (MCCS), which has been widely applied in many areas, such as electronic communications. This structure is also an analogy of the production line. The corresponding model is constructed based on the universal generating function (UGF) since it is a powerful tool in modeling a consecutively connected system. The proposed model can be used to evaluate the different productivities of different types of workers in different states and to realize the screening of the whole scheme through simulation. According to the proposed method, we obtained the optimal operation schedule, including the working time, rest time and allocation strategy for a production line system. Some examples are provided to illustrate the proposed method.