In this work, we report an efficient, one-pot and three-component synthesis of novel coumarin fused pyridine derivatives 4a–p. Heating the mixture of 4-hydroxycoumarins and ammonium acetate in DMF gave the corresponding 4-aminocoumarins, which subsequently went through Michael addition–cyclocondensation with α-azidochalcone derivatives to produce our desired products in high yields. The synthesized compounds 4a–p were evaluated for α-glucosidase inhibitory activity and all of them exhibited excellent in vitro yeast α-glucosidase inhibition with IC₅₀ values ranging from 101.0 ± 2.0 to 227.3 ± 1.4 μM when compared with the standard drug acarbose (IC₅₀ = 750.0 ± 1.5 μM). A kinetic study of the most potent compound 4i revealed that it inhibited α-glucosidase in a competitive mode. A docking study of the most active compounds 4i, 4h, and 4j was also performed.