A series of tetrahydropyrimidinyl-substituted benzimidazoles attached to various aliphatic or aromatic residues <i>via</i> phenoxymethylene were synthesised to investigate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. The influence of the type of substituent at the C-3 and C-4 positions of the phenoxymethylene linker on the antibacterial activity was observed, showing that the aromatic moiety improved the antibacterial potency. Of all the evaluated compounds, benzoyl-substituted benzimidazole derivative 15a was the most active compound, particularly against the Gram-negative pathogens <i>E. coli</i> (MIC = 1 μg mL<sup>-1</sup>) and <i>M. catarrhalis</i> (MIC = 2 μg mL<sup>-1</sup>). Compound 15a also exhibited the most promising antibacterial activity against sensitive and resistant strains of <i>S. pyogenes</i> (MIC = 2 μg mL<sup>-1</sup>). Significant stabilization effects and positive induced CD bands strongly support the binding of the most biologically active benzimidazoles inside the minor grooves of AT-rich DNA, in line with docking studies. The predicted physico-chemical and ADME properties lie within drug-like space except for low membrane permeability, which needs further optimization. Our findings encourage further development of novel structurally related 5(6)-tetrahydropyrimidinyl substituted benzimidazoles in order to optimize their antibacterial effect against common respiratory pathogens.