Reconfigurable manufacturing systems focus on part family products with its customized flexibility. The characteristics of reconfigurable manufacturing systems help in rapid change of system and cost-effective manufacturing of products. Reconfigurable manufacturing systems can be modified both physically by changing layout, machines and material handling devices and logically by changing route, schedule, planning and so on, which is easy for implementation in reconfigurable manufacturing systems compare to other manufacturing systems. This article aims at configuration selection of a single-product flow-line reconfigurable manufacturing systems using ant colony optimization approach consisting of two phases. In the first phase, priority-based encoding technique is used to find feasible operation clusters, and the second phase uses ant colony optimization technique for minimizing the capital cost of the reconfigurable manufacturing systems. A case study is illustrated with the proposed approach by developing a tool box in MATLAB software. The approach is validated by finding 10-best configurations with the consideration of minimum capital cost. The results are also supported by convergence curve derived by the software.