Seven new ophiobolins (1-5, 12, and 14) along with the 11 known analogues (6-11, 13, 15-18) were isolated from the ethyl acetate extracts of the liquid and solid cultures of the mangrove fungus Aspergillus ustus 094102. The structures including the absolute configurations of the seven new compounds were elucidated by spectroscopic analysis, chemical methods, and quantum ECD calculations. Compounds 4-8 and 11-15 showed cytotoxicities against the G3K, MCF-7, MD-MBA-231, MCF/Adr, A549, and HL-60 human cancer cell lines with the IC50 values ranging from 0.6 to 9.5 μM.