Sarcotragusolides A-D (<b>1</b>-<b>4</b>), four new butenolide sesterterpenes featuring a rare methyl-transferred 6/6/6-tricyclic fused ring system with a butyrolactone moiety, and echinohalimane B (<b>8</b>), an unprecedented monocyclic diterpenoid featuring a 2,7-ring-opened halimane-type skeleton, were isolated from the sponge <i>Sarcotragus</i> sp. A γ-hydroxybutenolide sesterterpene derivative (<b>5</b>), a new scalarane sesterterpene (<b>7</b>), a new subersin-type diterpenoid (<b>10</b>), and two known terpenoids were also isolated and identified. The discovery of sarcotragusolides C and D (<b>3</b> and <b>4</b>) with an unprecedented inversion of configuration implied a distinct biosynthetic pathway. The structures of these compounds were elucidated based on their spectroscopic data, single-crystal X-ray diffraction, chemical derivatization, and quantum chemical calculations. Compounds <b>1a</b>, <b>1b</b>, and <b>2</b> presented modest cytotoxic activities against several human cancer cell lines.