Some new benzoxazinonylhydrazone analogs derived from substituted benzaldehydes and benzoxazin-3(4H)-one pharmacophore have been synthesized by simple and efficient methods, using ultrasound (US) irradiations as well as conventional thermal heating (CTH). The treatment of the benzoxazinonylhydrazide (3) with the corresponding aromatic aldehyde, resulted in the formation of benzoxazinonylhydrazones (4a–4f) in good yields and short reaction times. The proposed structures of the obtained hydrazone compounds were identified and elucidated on the basis of FT-IR and nuclear magnetic resonance (1H-NMR and 13C-NMR) spectroscopy. The synthesized compounds were screened in vitro for their antibacterial and antifungal activities against three types of bacteria (S. aureus, E. coli, P. aeruginosa) and one type of fungi (C. albicans), respectively, by disc diffusion method. All of these hydrazone compounds exhibited remarkable antifungal activity and very moderate antibacterial activity.