A phytochemical study of the fungus Quambalaria cyanescens led to the isolation of one new natural compound (1), along with four known compounds (2–5). The structures of the isolated metabolites were elucidated based on spectroscopic and spectrometric techniques. The fatty acid composition of Q. cyanescens was determined by GC/MS and found to consist of stearic, myristic, lauric, linoleic, cis-vaccenic, oleic, and pentadecanoic acids. All the isolated compounds were evaluated for their antimicrobial, antimalarial, and antileishmanial activities.