The essential oil from the leaves of Annona sylvatica (EOAS) was extracted by hydrodistillation, and the analysis was performed by gas chromatography-mass spectrometry. The main compounds identified in the EOAS were sesquiterpenes, such as hinesol, z-caryophyllene, β-maaliene, γ-gurjunene, silphiperfol-5-en-3-ol, ledol, cubecol-1-epi, and muurola-3,5-diene. Oral administration of the EOAS (20 and 200 mg/kg) and subcutaneous injection of dexamethasone (0.5 mg/kg, reference drug) significantly inhibited carrageenan- and complete Freund's adjuvant-induced mouse paw edema. The anticancer activity the EOAS showed growth inhibitory activity on all cell lines when administered in a high concentration. The EOAS inhibited the growth of human cancer cell lines with GI(50) values in the range of 36.04-45.37 μg/mL on all of the cell lines tested. This work describes for the first time the anti-inflammatory and anticancer effects of the essential oil of A. sylvatica and its composition. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side-effects, the present results may have clinical relevance and open new possibilities for the development of novel anti-inflammatory and anticancer drugs.