Abstract The paper is aimed to develop a high performance rotary solid desiccant cooling system using a novel compound desiccant wheel (DW). The unique feature of the desiccant wheel is that it can work well under a lower regeneration temperature and have a higher dehumidification capacity due to the contribution of the new compound desiccant materials. Experimental results indicate that the novel desiccant wheel under practical operation can remove more moisture from the process air by about 20–40% over the desiccant wheel employing regular silica gel. A mathematical model that is used to predict the system performance has been validated with the test results. By integrating the desiccant wheel with evaporative cooling, heat recovery and heating for regeneration sections, a solid desiccant cooling system can be formed. Simulation results show that because of the use of the new compound desiccant, the desiccant cooling system can work under much lower regeneration temperature and have a relative high COP, thus low grade thermal energy resources, such as solar energy, waste heat, etc., can be efficiently utilized to drive such a cooling cycle.