After studying at Wadham College, Oxford, and Trinity College, Cambridge, Childers immigrated to Australia in 1850, entered the civil service, and in 1856 became a Cabinet member in the newly created parliamentary government of the state of Victoria. Returning to London in 1857 as agent general for Victoria, Childers soon was involved in British politics and business.

Elected a Liberal member of Parliament in 1860, he became financial secretary to the Treasury (1865–66), where his ability impressed Gladstone. In Gladstone's first ministry Childers was first lord of the Admiralty (1868–71) and chancellor of the duchy of Lancaster (1872–73). He returned to office with Gladstone in 1880, serving as secretary for war (to 1882) and then as chancellor of the Exchequer. His budgets were well received until 1885, when proposals for increased taxation contributed to the fall of a divided and unpopular government.

In the 1885 election Childers lost his seat in Parliament because of his advocacy of Irish Home Rule, but he was elected for another constituency in 1886 and was appointed home secretary in Gladstone's brief third ministry (February–July 1886). Childers retired from Parliament in 1892.