This paper seeks to gain an in-depth understanding of the seismic behavior of oval hollow section (OHS) beam-columns through experimental and numerical investigations. Quasi-static tests on nine OHS beam-column specimens with varying tube thicknesses, axial load ratios and bending directions are conducted, where the failure mode, yield/ultimate strength, ductility, and energy dissipation-related quantities are discussed in detail. Following the experimental program, a numerical study on a total of 360 OHS beam-column models with broadened section and material parameters is further conducted, and design recommendations for OHS beam-columns subjected to seismic conditions are proposed. Among other findings, the study reveals that local buckling at the fixed base is the governing failure mode for the considered members, but the failure mechanism varies under different bending directions. The flat web plate of the OHS is a critical area which is prone to local buckling, although stable post-buckling behavior can be exhibited. Earlier local buckling and more severe damage to the column base are induced when the axial load increases, resulting in decreased ductility. The plastic moment resistance is better mobilized with the increase in the tube thickness and when under major axis bending. The parametric study finally leads to practical ductility-oriented and strength-oriented design curves, where both least-square regression and lower-bound solutions are provided.