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Deep and slender wide-flange steel beam-columns are commonly used in steel special moment frames in North America, providing large moment-of-inertia while minimizing column steel weight. However, they are vulnerable to local and global geometric instabilities under lateral drift demands and compressive axial load. An experimental program was conducted to investigate the cyclic behavior of 10 full-scale deep beam-columns under unidirectional and bidirectional lateral loading protocols. The tests utilized a 6 degrees-of-freedom control system to simulate the flexibility of the beam-to-column connection. A corroborating finite element analytical study was also conducted to quantify the effects of local and global slenderness ratios, lateral loading protocol, and boundary conditions on the column's hysteretic behavior. The study found that bidirectional lateral deformations coupled with compressive axial load can affect the overall dynamic stability of steel beam-columns, and out-of-plane forces exerted at the top of the column due to twisting and global buckling are essential to properly design the lateral bracing of steel beam-columns.