Synthesis, structural characterization, and biological activity studies of novel pyrido[2,3-d]pyrimidines (10a-h, 11a-h) are described. Cyclization of cynoacetamides (4, 5) with malonitrile (7) and aldehyde (6a-h) via Hantzsch pyridine synthesis afforded cyanopyridones (8a-h, 9a-h), which on cyclization with formic acid under microwave conditions led to the final product. All the reactions are significantly faster and the isolated yields are remarkably higher in microwave conditions compared to the conventionally heated reactions. The compounds were tested in vitro for their antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtillus, Staphylococcus aureus, and Micrococcus luteus and antifungal activity against Trichphyton longifusus, Candida albicans, Microsporum canis, Fusarium solani. Compounds 10b, 10e, 11b and 11e exhibited good antibacterial and antifungal activities compared with standards.