His first academic appointment was at the University of Adelaide and then in 1958 he rejoined Dwyer at the Australian National University.
Sargeson was best known as a coordination chemist with an interest in bioinorganic chemistry.  In early work with Dwyer and throughout his career, he studied stereochemistry.  His research group investigated the reactions of amine ligands, culminating in the synthesis of the clathrochelates called "sepulchrates".