Considerable studies have been carried out on the seismic performance of fiber-reinforced polymer (FRP) retrofitted reinforced concrete (RC) columns. However, research on the seismic performance of FRP-retrofitted RC columns under lateral loading in different directions remains limited. This paper presents an experimental investigation on both un-retrofitted and carbon FRP (CFRP) retrofitted rectangular RC columns with an emphasis on the effect of the directions of lateral loading on the seismic performance of the columns. A total of ten large-scale cantilever rectangular RC columns were constructed and five of them were retrofitted with CFRP wraps at the potential plastic hinge regions. The overall performance of each specimen is examined in terms of damage evolution, lateral load-displacement hysteretic behavior, lateral strength, ductility capacity, stiffness degradation, and energy dissipation. The direction of lateral loading is found to have significant influence on the seismic performance of both un-retrofitted and CFRP-retrofitted rectangular RC columns. It is also found that the shear strength of the un-retrofitted and FRP-retrofitted rectangular RC columns in nonprincipal directions can be predicted based on the lateral strength in the principal directions by the ellipse equation.