Three new C<sub>21</sub> pregnane steroids, chonemorphols A-C (1, 3, and 4), 11 new C<sub>21</sub> steroidal glycosides, chonemorphosides A-K (2 and 5-14), and 11 known compounds (15-25) were obtained from the vines and leaves of Chonemorpha megacalyx Pierre. Their structures were established using extensive spectroscopic data. The X-ray crystallographic data of 1 and 3 permitted definition of their absolute configurations. Notably, 1 and 2 possessed an uncommon 6/5/6/5/5-fused steroidal ring system. Compound 7 displayed significant cytotoxicity against several cancer cell lines with IC<sub>50</sub> values of 2.0-3.6 μM.