Central to Alzheimer's disease is the misfolding of amyloid-beta (Aβ) peptide, which generates an assorted population of amorphous aggregates, oligomers and fibres. Metal ion homoeostasis is disrupted in the brains of sufferers of Alzheimer's disease and causes heightened Alzheimer's disease phenotype in animal models. In the present study, we demonstrate that substochiometric Cu²⁺ affects the misfolding pathway of Aβ₁₋₄₀, and the more toxic Aβ₁₋₄₂, in markedly different ways. Cu²⁺ accelerates Aβ₁₋₄₀ fibre formation. In contrast, for Aβ₁₋₄₂, substoichiometric levels of Cu²⁺ almost exclusively promote the formation of oligomeric and protofibrillar assemblies. Indeed, mature Aβ₁₋₄₂ fibres are disassembled into oligomers when Cu²⁺ is added. These Cu²⁺ stabilized oligomers of Aβ₁₋₄₂ interact with the lipid bilayer, disrupting the membrane and increasing permeability. Our investigation of Aβ₁₋₄₀/Aβ₁₋₄₂ mixtures with Cu²⁺ revealed that Aβ₁₋₄₀ neither contributed to nor perturbed formation of Aβ₁₋₄₂ oligomers, although Cu²⁺-Aβ₁₋₄₂ does frustrate Cu²⁺-Aβ₁₋₄₀ fibre growth. Small amounts of Cu²⁺ accentuate differences in the propensity of Aβ₁₋₄₀ and Aβ₁₋₄₂ to form synaptotoxic oligomers, providing an explanation for the connection between disrupted Cu²⁺ homoeostasis and elevated Aβ₁₋₄₂ neurotoxicity in Alzheimer's disease.