In order to compare the utility of standard solvent partitioning (SSP) versus accelerated solvent extraction (ASE), a series of experiments were performed and evaluated. Overall yields, solvent consumption, processing time, and chemical stability of the fractions obtained by both methods were compared. Five marine sponges were selected for processing and analysis containing 12 structurally distinct, bioactive natural products. Extracts generated using SSP and ASE were assessed for chemical degradation using comparative LC MS-ELSD. The extraction efficiency (EE) of the ASE apparatus was 3 times greater than the SSP method on average, while the total extraction yields (TEY) were roughly equivalent. Furthermore, the ASE methodology required only 2 h to process each sample versus 80 h for SSP, and the LC MS-ELSD from extracts of both methods appeared comparable. These results demonstrate that ASE can serve as an effective high-throughput methodology for extracting marine organisms to streamline the discovery of novel and bioactive natural products.