He was elected to the Victorian Legislative Assembly in 1892, and subsequently served as Solicitor-General under James Patterson, and Attorney-General under George Turner and Alexander Peacock.

He became Attorney-General of Australia in 1905, under Alfred Deakin, but the following year left politics in order to become a justice of the High Court.

Isaacs was often in the minority in his early years on the court, particularly with regard to federalism, where he advocated the supremacy of the Commonwealth Government.

The balance of the court eventually shifted, and he famously authored the majority opinion in the Engineers case of 1920, which abolished the reserved powers doctrine and fully established the paramountcy of Commonwealth law.

In 1930, Prime Minister James Scullin appointed Isaacs as Chief Justice, in succession to Sir Adrian Knox.

Seeking better prospects, Alfred left Poland and worked his way across Germany, spending some months in Berlin and Frankfurt.

After news of the 1851 Victorian gold rush reached England, Australia became a very popular destination and the Isaacs decided to emigrate.

[1] Some time after arriving the Isaacs moved into a cottage and shopfront in Elizabeth Street, Melbourne, where Alfred continued his tailoring.

Here he excelled academically, particularly in arithmetic and languages, though he was a frequent truant, walking off to spend time in the nearby mining camps.

[7] While employed at the State School, Isaacs had his first experience of the law, as an unsuccessful litigant in an 1875 County Court case.

However, he was not elected to the committee drafting the constitution; Alfred Deakin attributed this failure to "a plot discreditable to all engaged in it" and thought that this antagonizing and humiliating snub sharpened Isaacs's "tendency to minute technical criticism ... so as to bring him not infrequently into collision" with the committee.

[6][11] Isaacs was elected to the first federal Parliament in 1901 to the seat of Indi as a critical supporter of Edmund Barton and his Protectionist government.

[6] He was one of a group of backbenchers pushing for more radical policies and he earned the dislike of many of his colleagues through what they saw as his aloofness and rather self-righteous attitude to politics.

In April 1930, the Labor Prime Minister, James Scullin, appointed the 75-year-old Isaacs as chief justice, succeeding Sir Adrian Knox.

While Isaacs was personally esteemed, public opinion divided strongly over whether a governor-general should be an Australian, with perceived risks of local political bias.

[15] Isaacs married Deborah "Daisy" Jacobs, daughter of a tobacco merchant, at her parents' home in St Kilda on 18 July 1888.

Following the King David Hotel bombing in 1946, he wrote that "the honour of Jews throughout the world demands the renunciation of political Zionism".

Isaacs's main objections to Political Zionism were: Isaacs said "the Zionist movement as a whole...now places its own unwarranted interpretation on the Balfour Declaration, and makes demands that are arousing the antagonism of the Muslim world of nearly 400 millions, thereby menacing the safety of our Empire, endangering world peace and imperiling some of the most sacred associations of the Jewish, Christian, and Muslim faiths.

The Commonwealth government accorded him a state funeral, held on 13 February, and he was buried in Melbourne General Cemetery after a synagogue service.

At a redistribution in November 1968, the electorate was abolished and a separate Division of Isaacs was created in the south-eastern suburbs of Melbourne.