An experimental investigation was carried out to study the effects of single and multiple vortex generators (VGs) on the mean velocity, turbulence levels, and surface temperature distributions in a square channel. The flow and heat transfer in the wake of VGs were characterized using particle image velocimetry (PIV) and infrared (IR) thermography. Measurements were performed in the wake regions of VGs, where the counter-rotating vortex pairs (CVPs) were dominant. Inclination angle and taper angle of VGs, spacing-to-width ratio (STW), and streamwise spacing between rows of VGs (S) were varied to understand the effects on flow and heat transfer characteristics. Results reveal a distinct impact of the VGs and layouts on the vortical flow and local convective heat transfer phenomena. The measurements clearly show that configuration parameters such as inclination angle, spacing-to-width ratio, streamwise spacing, and arrangement of multiple VGs are factors in the optimum heat transfer performance applicable to a wide range of thermal management systems.