The first Vice-Chancellor in the current sense of the University's full-time chief executive and its academic and administrative head was appointed in 1948. There had been Vice-Chancellors previously, but they were deputies to the Chancellor on the University Council (since 1946 the title for that role has been Pro-Chancellor).
- 1948–1953
- Sir Robert Stevenson Aitken MD(NZ) DPhil(Oxon) HonLLD(Dal) (Melb) (Panj) (McG) (Nfld) (Penn) (Aberd) (Otago) HonDSc(Syd) HonDCL(Oxon) FRCP FRCPEd FRACP
- 1953–1963
- Frederick George Soper CBE PhD DSc(Wales) HonDSc(Otago) FRSNZ CChem FRSC HonFNZIC
- 1964–1966
- Arthur Beacham OBE BA(Wales) MA(Liv) PhD(Belf) HonLLD(Otago)
- 1967–1973
- Robert Martin Williams CBE MA(NZ) BA PhD(Cantab) HonLLD(Otago)
- 1973–1993
- Sir Robin Orlando Hamilton Irvine MD(NZ) Dr h c(Edin) HonLLD(Otago) FRCP FRACP FRSA FNZIM
- 1994–2004
- Dr Graeme Fogelberg CNZM BCom(NZ) MCom(Well) MBA PhD (W Ont) HonLLD(Otago) FInstD
- 2004–2011
- Sir David Christopher Graham Skegg, KNZM OBE BMedSc MB ChB HonLLD(Otago) DPhil(Oxf) FFPHM FAFPHM FRSNZ
- 2011–2021
- Professor Harlene Hayne, ONZM BA HonDSc(Colorado College) MS PhD(Rutgers) HonLLD (Otago) FRSNZ
- 2022–2023
- Professor David Roger Murdoch MB ChB MD(Otago) MSc(Lond) DTM&H(Liv) FRACP FRCPA FFSc(RCPA)
- Acting from 2021–2022, 2023–2024
- Professor Helen D Nicholson BSc(Hons) MB ChB MD(Brist)