This paper reports a series of heterodivalent linked macrocyclic β-sheets 6 that are not only far more active against amyloid-β (Aβ) aggregation than their monovalent components 1a and 1b but also are dramatically more active than their homodivalent counterparts 4 and 5. The macrocyclic β-sheet components 1a and 1b comprise pentapeptides derived from the N- and C-terminal regions of Aβ and molecular template and turn units that enforce a β-sheet structure and block aggregation. Thioflavin T fluorescence assays show that heterodivalent linked macrocyclic β-sheets 6 delay Aβ(1-40) aggregation 6-8-fold at equimolar concentrations and substantially delay aggregation at substoichiometric concentrations, while homodivalent linked macrocyclic β-sheets 4 and 5 and monovalent macrocyclic β-sheets 1a and 1b only exhibit more modest effects at equimolar or greater concentrations. A model to explain these observations is proposed, in which the inhibitors bind to and stabilize the early β-structured Aβ oligomers and thus delay aggregation. In this model, heterodivalent linked macrocyclic β-sheets 6 bind to the β-structured oligomers more strongly, because N-terminal-derived component 1a can bind to the N-terminal-based core of the β-structured oligomers, while the C-terminal-derived component 1b can achieve additional interactions with the C-terminal region of Aβ. The enhanced activity of the heterodivalent compounds suggests that polyvalent inhibitors that can target multiple regions of amyloidogenic peptides and proteins are better than those that only target a single region.