Abstract The regioselective synthesis of a new series of pyrazolo[5,1‐ b ]quinazolines was carried out using a three‐component protocol. The protocol involved the reaction of the appropriate benzaldehydes, dimedone, and 1 H ‐pyrazole‐ 3,5‐diamine in DMF at 150 °C. Using a similar protocol, three additional series of bis(pyrazolo[5,1‐ b ]quinazolines), linked to different spacers, were prepared utilizing the respective bis(aldehydes). The new products showed a wide spectrum of antibacterial activity against six different the American Type Culture Collection (ATCC) bacterial strains. In general, p‐ xylene‐linked bis(pyrazolo[5,1‐ b ]quinazolines) had good antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values up to 8.3 and 16.6 μM, respectively. Additionally, (4‐nitrophenyl)‐linked pyrazolo[5,1‐ b ]quinazoline had the best antibacterial activity with MIC/MBC values up to 2.1/4.3 μM. The Salmonella typhimurium reverse mutation assay (Ames mutagenicity test) was used to conclude that the (4‐nitrophenyl)‐linked product was not mutagenic to the Salmonella strains. Both the drug‐likeness model score and the SwissADME predict the (4‐nitrophenyl)‐linked product‘s good physicochemical properties, and drug likeness.