In this work, we have synthesised and characterised a series of tetralactam macrocycle transporters based on the previously reported tetralactam 4a and studied the Cl -binding, Cl -transport, F -transport, and transport selectivity properties of each. Throughout the studies, the tetralactams containing fluorinated isophthalamide-substituents displayed the highest transport activities, but the aromatic linkers had the largest impact on anion transport. In all cases, the transporters containing the 4,5difluorophenylene-linker linker displayed the strongest binding and highest transport activities. 1 H-NMR Cl -binding studies demonstrated that the series was capable of moderate 1:1 host:guest binding, which was ideal for efficient anion recognition, capture, and release during transport. An important milestone was achieved when testing 2c and 3c using the ISE-based Cl -/NO3 -exchange transport assay, with results showing that they are the two most active transporters ever recorded using this method. Mechanistic transport studies revealed that the series primarily operates via an electroneutral H + /Cl -co-transport mechanism. Significantly, comparing the most potent transporters 2c and 3c to the best natural anionophore, prodigiosin, in the HPTS transport assay showed a 2.2-and 1.4-fold enhancement in H + /Cl -transport activity, respectively. The previously most active synthetic H + /Cl -transporter was analysed using an adjusted HPTS transport assay. This assay was recreated, and compounds 2c and 3c displayed a 3.1 and 1.2-fold enhancement in transport activity over this transporter, respectively. Thus, 2c and 3c are among the most active Cl -transporters ever tested in vesicular assays. Finally, we analysed the F -/Cl -antiport ability of the entire series using a recently developed assay by Butler, Valkenier, and co-workers. Hill analysis showed that these transporters are also extremely active F -transporters, with 1c, 2c, 3c, and 4c producing the highest F -transport activities across the series.