In this study, the buoyancy-driven fluid flow and heat transfer in a differentially-heated rectangular cavity filled with the TiO2-water nanofluid is investigated numerically. The left and the top walls of the cavity are maintained at constant temperatures Th and Tc, respectively, with Th > Tc. The enclosure’s right and bottom walls are kept insulated. The governing equations are discretized using the finite volume method. A proper upwinding scheme is employed to obtain stabilized solutions for high Rayleigh numbers. Using the developed code, a parametric study is undertaken, and the effects of pertinent parameters, such as, the Rayleigh number, the aspect ratio of the cavity and the volume fraction of the nanoparticles on the fluid flow and heat transfer inside the cavity are investigated. It is observed from the results that by increasing the volume fraction of the nanoparticles, the mean Nusselt number of the hot wall increases for the shallow cavities; while, the reverse trend occurs for the tall cavities. Moreover, the heat transfer enhancement utilizing nanofluid is more effective at Ra = 103.