A cooling system for providing conditioned air to a facility includes a chiller or other cooling subsystem, a cooling tower subsystem and one or more air handling units or process cooling units. The cooling subsystem may advantageously include one or more chillers (e.g., variable speed chillers, constant speed chillers, absorption chillers, etc.) and chilled fluid pumps. The cooling tower subsystem includes one or more cooling tower units and condenser fluid pumps. In some implementations, the air handling unit has a cooling coil and a variable volume fan. In some implementations, direct expansion (DX) cooling systems comprise compressors, evaporators and air-cooled, water-cooled or evaporatively-cooled condensing systems. Such systems can be controlled to reduce energy waste, improve occupant comfort and/or improve the thermal characteristics of the process cooling unit. The cooling system further comprises a control system which is configured to evaluate a cooling load value at the air handling unit and use the cooling load value to calculate at least one operational setpoint. The operational setpoint may advantageously be selected to improve the energy efficiency of the overall cooling system.