Author summary Cellular complexity necessitates an equally complex network of courier proteins to internalise, sort, and deliver biologically useful metals like copper. These relay systems negotiate a landscape of metal-binding sites through handshake–handoff interactions, but the mechanisms that impart a necessary transience are often not clear. Superoxide dismutase-1 (SOD1) is one of the most abundant human proteins and is an important part of our antioxidant, redox signalling and respiratory control mechanisms. If newly synthesised SOD1 is not correctly processed by the addition of copper, zinc, and an unusual disulphide bond, it will remain inactive or can misfold, as is the case in some neurodegenerative diseases. Here, we discover the mechanisms that govern SOD1 maturation and stabilisation through interaction with the chaperone protein hCCS. Conservation of our proposed mechanism across eukaryotes indicates it developed very soon after the gene duplication event that separated SOD1 and CCS coding sequences. SOD1 stability appears to have been quickly traded at the expense of CCS following the dawn of eukaryotic life, in order to efficiently produce this important enzyme.