This paper reports theoretical and numerical analysis of fluid flow and heat transfer in a cascade electro-osmotic flow (EOF) micropump for chip cooling. A simple analytical model is developed to determine the temperature distribution in a two-dimensional (2D) single channel EOF micropump with forced convection due to a voltage difference between both ends. Numerical simulations are performed to determine the temperature distribution in the domain which is compared with that predicted by the model. A novel cascade EOF micropump with multiple microchannels in series and parallel and with an array of interdigitated electrodes along the flow direction is proposed. The simulations predict the maximum flow rate and pressure capability of one single stage of the micropump and the analytical model employs equivalent circuit theory to predict the total flow rate and back pressure. Each stage of the proposed micropump comprises sump and pump regions having opposing electric field directions. The various design parameters of the micropump includes the height of the pump and sump (h), number of stages (n), channel width (w), thickness of the channel wall or fin (r), and width ratio of the pump and sump (s:p) regions. Numerical simulations are performed to predict the effects of these design parameters on the pump performance which is compared with that predicted by the analytical model. The micropump is used for cooling cooling of an Intel® CoreTM i5 chip which produces a maximum heat of 95 W over an area of 3.75 × 3.75 cm. Based on the parametric studies a design for the cascade EOF micropump is proposed which provides a maximum flow rate of 14.16 ml/min and a maximum back pressure of 572.5 Pa to maintain a maximum chip temperature of 310.63 K.