The cross flow heat exchanger is at the heart of most cooling systems for data centers. Air/Water or air/refrigerant heat exchangers are the principal component in Central Room Air Conditioning (CRAC) units that condition data room air that is delivered through an underfloor plenum. Liquid/air heat exchangers are also increasingly deployed in close-coupled cooling systems such as rear door heat exchangers, in-row coolers, and overhead coolers. In all cases, the performance of liquid/air heat exchangers in both steady state and transient scenarios are of principal concern. Transient scenarios occur either by the accidental failure of the cooling system or by intentional dynamic control of the cooling system. In either scenario, transient boundary conditions involve time-dependent air or liquid inlet temperatures and mass flow rates that may be coupled in any number of potential combinations. Understanding and characterizing the performance of the heat exchanger in these transient scenarios is of paramount importance for designing better thermal solutions and improving the operational efficiency of existing cooling systems. In this paper, the transient performance of water to air cross flow heat exchangers is studied using numerical modeling and experimental measurements. Experimental measurements in 12 in. × 12 in. heat exchanger cores were performed, in which the liquid (water) mass flow rate or inlet temperature are varied in time following controlled functional forms (step jump, ramp). The experimental data were used to validate a transient numerical model developed with traditional assumptions of space averaging of heat transfer coefficients, and volume averaging of thermal capacitances. The complete numerical model was combined with the transient effectiveness methodology in which the traditional heat exchanger effectiveness approach is extended into a transient domain, and is then used to model the heat exchanger transient response. Different transient scenarios were parametrically studied to develop an understanding of the impact of critical variables such as, the fluid inlet temperature variation and the fluid mass flow rate variation, and a more comprehensive understanding of the characteristics of the transient effectiveness. Agreement between the novel transient effectiveness modeling approach and the experimental measurements enable use of the models as verified predictive design tools. Several studies are designed based on the practical problems related to data center thermal environments and the results are analyzed.