Cavalier-Smith was born on 21 October 1942 in London. His parents were Alan Hailes Spencer and Mary Maude Cavalier-Smith. He was educated at Norwich School, Gonville and Caius College, Cambridge and King's College London. He was under the supervision of Sir John Randall for his PhD thesis between 1964 and 1967; his thesis was entitled "Organelle Development in Chlamydomonas reinhardii". From 1967 to 1969, he was a guest investigator at Rockefeller University. He became Lecturer of biophysics at King's College London in 1969. He was promoted to Reader in 1982. In 1989 he was appointed Professor of botany at the University of British Columbia. In 1999, he joined the University of Oxford, becoming Professor of evolutionary biology in 2000.
Cavalier-Smith has written extensively on the taxonomy and classification of protists. One of his major contributions to biology was his proposal of a new kingdom of life: the Chromista. He also introduced a new group for primitive eukaryotes called the Chromalveolata, as well as Opisthokonta, Rhizaria, and Excavata. Though fairly well known, many of his claims have been controversial and have not gained widespread acceptance in the scientific community to date. His taxonomic revisions often lead to changes in the overall classification of all life forms.
Cavalier-Smith's first major classification system was the division of all organisms into eight kingdoms. In 1981, he proposed that by completely revising Robert Whittaker's Five Kingdom system, there could be eight kingdoms: Bacteria, Eufungi, Ciliofungi, Animalia, Biliphyta, Viridiplantae, Cryptophyta, and Euglenozoa. In 1993, he revised his system particularly in the light of the general acceptance of Archaebacteria as separate group from Bacteria. In addition, some protists lacking mitochondria were discovered. As mitochondria were known to be the result of the endosymbiosis of a proteobacterium, it was thought that these amitochondriate eukaryotes were primitively so, marking an important step in eukaryogenesis. As a result, these amitochondriate protists were separated from the protist kingdom, giving rise to the, at the same time, superkingdom and kingdom Archezoa. This was known as the Archezoa hypothesis. The eight kingdoms became: Eubacteria, Archaebacteria, Archezoa, Protozoa, Chromista, Plantae, Fungi, and Animalia. However, kingdom Archezoa is now defunct. He now assigns former members of the kingdom Archezoa to the phylum Amoebozoa.
By 1998, Cavalier-Smith had reduced the total number of kingdoms from eight to six: Animalia, Protozoa, Fungi, Plantae, Chromista and Bacteria. Nevertheless, he had already presented this simplified scheme for the first time on his 1981 paper and endorsed it in 1983. Five of Cavalier-Smith's kingdoms are classified as eukaryotes as shown in the following scheme:
Eubacteria
Neomura
*Archaebacteria
*Eukaryotes
**Kingdom Protozoa
** Unikonts
***Kingdom Animalia
***Kingdom Fungi
** Bikonts
***Kingdom Plantae
***Kingdom Chromista
The kingdom Animalia was divided into four subkingdoms: Radiata, Myxozoa, Mesozoa, and Bilateria. He created three new animal phyla: Acanthognatha, Brachiozoa, and Lobopoda and recognised a total of 23 animal phyla. Cavalier-Smith's 2003 classification scheme:
Cavalier-Smith and his collaborators revised the classification in 2015, and published it in PLOS ONE. In this scheme they reintroduced the division of prokaryotes into two kingdoms, Bacteria and Archaea. This is based on the consensus in the Taxonomic Outline of Bacteria and Archaea and the Catalogue of Life.