Talarolactones A-G (1-7), seven novel α-pyrone adducts with unprecedented scaffolds, together with two pairs of α-pyrone monomers [(±)-8 and (±)-9)] were isolated from Talaromyces adpressus. Compounds 1-7 are highly modified α-pyrone dimers with a 4,7,7,8-tetrasubstitued 5,6,7,8-tetrahydro-2H-chromen-2-one. Compounds 5 and 6 possessed a significant NO production inhibitory effect, with IC50 values of 2.3 ± 0.1 and 3.7 ± 0.3 μM, respectively. Plausible biosynthetic pathways were proposed and supported by the results of heterologous expression experiments.