The essential oil of Croton sonderianus Muell. Arg. (Euphorbiaceae) contains a- and β-pinene, camphene, myrcene, limonene, γ-terpinene, camphor, terpinen-4-ol, copaene, β-elemene, α-gurjunene, cyperene, β-caryophyllene, thujopsene, trans-β-farnesene, γ- and δ-cadinene, γ-muurolene, palustrol, guayazulene, and a novel benzofuran sesquiterpene named marmelerin (1, dihydro-1,2,5,8-tetramethyl-6H-indeno[5,4-b]furan). Isolated from the residue of the fractionally distilled essential oil and the nonpolar fraction of the hexanic root extract, marmelerin represents the first natural sesquiterpene with a tetrasubstituted furan ring. Its structure was established using UV, IR, MS, 1H/13C NMR (including APT, SFORD, and selective decoupling), hydrogenation to a dihydroderivative, and a two-dimensional 13C INADEQUATE experiment to determine carbon-carbon connectivities. The INADEQUATE data unequivocally confirmed the structure as 1, supporting an isoprene rule-based biogenetic route. Evaluation of marmelerin’s antimicrobial activity showed it lacked such activity, despite the plant’s extracts previously demonstrating antimicrobial properties.