Modern tall and irregular buildings have become increasingly slender and have columns with high axial force, which can pose a serious risk to the seismic safety of these structures. However, existing experimental studies on slender reinforced concrete (RC) columns under high axial force are limited due to the restrictions of testing facilities. Most studies are based on small cross-section specimens bent in single curvatures and loaded monotonically. But these studies may not accurately reflect the realistic seismic behavior of full-scale double-curvature RC columns in buildings due to size effects. Therefore, the objective of this study is to provide new insights into the seismic performance of full-scale slender and large cross-section RC columns with various transverse reinforcement designs under a constant high axial load of up to 50% of the axial capacity. The full-scale specimens were tested in a double-curvature configuration under cyclic lateral displacement reversals and high axial loads. The results show that the tested slender columns experienced significant P-Δ moment magnification effects, with further drifts after yielding. This imposed a greater loading demand on the sections and destabilized the columns after peak loads. The robustly anchored transverse reinforcement improved seismic performance indicators, including strength retention and drift capacity, and reduced the P-Δ moment magnification experienced by slender columns, which enhances the stability index.