Fractionation of an aqueous extract from the aerial parts of <i>Ageratina grandifolia</i> yielded a new natural product, namely, 4-hydroxy-3-((<i>S</i>)-1'-angeloyloxy-(<i>R</i>)-2',3'-epoxy-3'-methyl)butylacetophenone (<b>1</b>), along with eight known compounds, including three flavonoids (<b>2</b>-<b>4</b>) and five chromenes (<b>5</b>-<b>9</b>). NMR data interpretation and DFT-calculated chemical shifts combined with DP4+ statistical and <i>J</i>-DP4 probability analyses allowed for the complete characterization of compound <b>1</b>. The presence of compound <b>1</b> in a plant that biosynthesizes 2,2-dimethylchromenes is noteworthy, because an epoxy derivative has long been postulated as the reaction intermediate from the prenylated <i>p</i>-hydroxyacetophenones to cyclic dimethylchromenes. So far, this key intermediate has not been isolated, due to its purported chemical instability. Thus, this is the first report of a potential epoxide intermediate, leading to any of the chromene constituents of this plant. Compounds <b>1</b>-<b>9</b> inhibited yeast α-glucosidase with IC<sub>50</sub> values ranging from 0.79 to 460 μM (acarbose, IC<sub>50</sub> = 278.7 μM). The most active compounds were quercetagetin-7-<i>O</i>-(6-<i>O</i>-caffeoyl-β-d-glucopyranoside (<b>3</b>) and 6-hydroxykaempferol-7-<i>O</i>-(6-<i>O</i>-caffeoyl-β-d-glucopyranoside (<b>4</b>). Kinetic analysis of <b>3</b> revealed its mixed-type inhibitor nature. Docking studies into the crystallographic structure of yeast α-glucosidase (pdb 3A4A) predicted that <b>3</b> and <b>4</b> bind at the catalytic site of the enzyme.