Three phenylspirodrimane-based meroterpenoids with novel scaffolds, namely chartarolides A-C (1–3), were isolated from a sponge (Niphates recondite) associated fungus Stachybotrys chartarum WGC-25C-6. Their structures were determined on the basis of comprehensive analyses of the spectroscopic data (IR, 1D and 2D NMR, HRESIMS), including the TDDFT-ECD calculation for the assignments of absolute configurations. The biogenetic generation of 1–3 through the conjunction of phenylspirodrimane and mollicellin-type analogues as the precursors was postulated. Chartarolides A-C exhibited significant cytotoxic activities against a panel of human tumor cell lines, and showed strong inhibitory activities against the human tumor related protein kinases of FGFR3, IGF1R, PDGFRb, and TrKB.