Chromatographic separation of a marine algal-derived endophytic fungus Penicillium chrysogenum AD-1540, which was isolated from the inner tissue of the marine red alga Grateloupia turuturu, yielded two new benzophenone derivatives, chryxanthones A and B (compounds 1 and 2, respectively). Their structures were undoubtedly determined by comprehensive analysis of spectroscopic data (1D/2D NMR and HRESIMS). The relative and absolute configurations were assigned by analysis of the coupling constants and time-dependent density functional theory (TDDFT) calculations of their electronic circular dichroism (ECD) spectra, respectively. Both compounds possessed an unusual dihydropyran ring (ring D) fused to an aromatic ring, rather than the commonly occurring prenyl moiety, and a plausible biosynthetic pathway was postulated. The cytotoxicities of compounds 1 and 2 were evaluated against six human cell lines, and both of the compounds demonstrated weak to moderate cytotoxicities with IC50 values ranging from 20.4 to 46.4 μM. These new compounds further demonstrate the potential of marine-derived fungi as an untapped source of pharmaceutical components with unique properties that could be developed as drug candidates.