Significance Bacterial ABC transporters typically mediate transport of substrates across the cytoplasmic membrane, using either alternating access or toppling-based mechanisms. The noncanonical ABC transporter MacB does not behave in this manner, but instead couples cytoplasmic ATP hydrolysis with periplasmic conformational changes that drive substrates from the periplasm to the extracellular space via the TolC exit duct. Here we describe the mechanotransmission mechanism of MacB in molecular detail by comparing ATP-bound and nucleotide-free structures. We further show that MacB shares its structural architecture with an entire superfamily of ABC transporters responsible for fundamental bacterial processes, including cell division and outer membrane biogenesis, suggesting a common mode of operation, and raise the possibility of targeting such proteins for the development of new antibiotics.