When water chillers are arranged in series-series counterflow (SSCF), the compressor lift of each chiller is decreased in comparison with that of water chillers in parallel. This means that the compressor power of SSCF chillers is lower than that of parallel chillers. In this paper, models of the main components in an air conditioning system were developed and verified to predict the behaviors of the whole system with respect to SSCF chillers. The results showed that performance was maximized with three SSCF chillers when the system was operated with normal set points. The performance was further improved to 26% and decreased with the number of SSCF chillers when the system was operated with optimal set points. The SSCF chiller system also demonstrated higher exergy efficiency regardless of the number of SSCF chillers. The irreversibility of components in SSCF chillers was rather low. However, the irreversibility of the cooling tower and cooling coil was slightly higher and lower, respectively, than those in the parallel chiller system.