He enrolled at the Middle Temple in London in 1849, but spent some of the following year teaching at Routledge's School, Bishop's Hull, Somersetshire.

He had some luck as a goldminer but contracted dysentery and moved back to town where he became a magistrate's clerk, first at Elephant Bridge, then Carisbrook and, in 1854, Maryborough.

From 1865 onwards Prendergast rose through series of national roles, from Member of Parliament, to Attorney-General and then Chief Justice of New Zealand and leading to his being knighted in November 1881.

In 1867 he resigned from the Legislative Council, his role as Crown solicitor in Otago and his law practice and moved north to Wellington.

Prendergast was appointed Chief Justice of New Zealand on 1 April 1875 on the advice of Sir Julius Vogel's government.

Prendergast's most notable judgement was Wi Parata v the Bishop of Wellington in 1877, a case involving Māori land in Porirua that was given to the Anglican Church for the purpose of building a school.

In his judgement, Prendergast took the view that "native" or "aboriginal" customary title, not pursuant to a Crown grant, could not be recognised or enforced by the courts, because the Treaty of Waitangi was a "simple nullity".

Prendergast's reasoning was both overturned and enhanced in 1941 when Te Heuheu Tukino v Aotea District Māori Land Board[6] was decided, where the Court ruled that the Treaty was seen as valid in terms of the transfer of sovereignty, but as it was not part of New Zealand statute law it was not binding on the Crown.

In 1901 he planted the Sitka Spruce on Campbell Island, which in February 2017 was recorded to have the 'golden spike' in nuclear testing in the 1950s and 1960s; it has been named as the 'World's loneliest tree'.