He received an MA from the University of Wales in 1930 for a dissertation on the Roman pottery from the 20th Legion's works at Holt (then in Denbighshire).

He became interested in the prehistory of Wales, and was involved in excavations at Pyle, Ludchurch, Corston Beacon and Llanboidy.

He met Audrey Williams in 1935, while preparing an exhibition in Swansea for the centenary of the Royal Institution of South Wales.

Grimes moved to Southampton in 1938 to become an assistant archaeology officer with the Ordnance Survey, and was quickly involved in the excavation of the newly discovered ship burial at Sutton Hoo the following year.

A highlight was the excavation of the London Mithraeum with Audrey Williams, which was discovered at a building site at Walbrook in 1954.

The unexpected discovery of a bust of Mithras on the last scheduled day of the excavation generated considerable press and public interest, debates in Parliament and discussion in the Cabinet.

Although Bucklersbury House was built over the site, Grimes succeeded in salvaging many of its finds and features including marble statuary attesting to the wealth of its congregation.

He continued his excavations in London after he succeeded V. Gordon Childe as director of the Institute of Archaeology and professor of archaeology at the University of London in 1956 (Wheeler had founded the Institute in 1937, and Childe became director after Wheeler resigned in 1946).

While Grimes was its director, the Institute moved from St John's Lodge in Regent's Park to new premises at Gordon Square.