The rise of bacterial resistance to common clinical antibiotics is calling for alternative approaches to synthesize new antibacterial drugs with high environmental biodegradability. One such approach is the use of microwave-assisted synthesis, which is a powerful green synthetic technique used increasingly to accelerate organic reactions. To discover new antibacterial compounds, we report the efficient synthesis of nineteen thiophene derivatives, five furan derivatives, and two thiazole derivatives, using Suzuki-Miyaura cross-coupling by microwave irradiation. Microwave irradiation conditions have reduced the reaction time, increased the yield and this method uses less organic solvent compared to conventional heating. Several compounds showed broad antibacterial activity. One compound, in particular, demonstrated significant antibacterial activity against Streptococcus pyogenes with a minimal inhibitory concentration of 0.097 µg/mL and against Salmonella enterica with a minimal inhibitory concentration of 0.78 µg/mL. The biodegradability of two furan derivatives with the best antibacterial activities and their effects on environmental bacteria were studied using the closed bottle test. This test proved that the two compounds were readily biodegradable without toxic effects on environmental bacteria present in wastewater treatment plants. Therefore our data demonstrated not only green synthesis but also environmental benignity due to the biodegradability of the novel antibacterials, which is a very desirable feature.