In 1872 Griffith was elected to the Queensland Legislative Assembly. Throughout his career he saw himself as a lawyer first and a politician second, and continued to appear at the Bar even when he was in office. In Parliament he gained a reputation as a liberal reformer. He was Attorney-General, Minister for Education and Minister for Works, and became leader of the liberal party in 1879. His great enemy was the conservative leader Sir Thomas McIlwraith, whom he accused (correctly) of corruption.
Griffith becamer Premier in 1883, holding office until 1888, and was knighted in 1886. He was regarded as a close ally of the labour movement. He introduced a bill to legalise trade unions, and declared that "the great problem of this age is not how to accumulate wealth but how to secure its more equitable distribution." In 1888 his government was defeated. In opposition he wrote radical articles for The Boomerang, William Lane's socialist newspaper.
But in 1890 Griffith suddenly betrayed his radical friends and became Premier again at the head of an unlikely alliance with McIlwraith, the so-called "Griffilwraith." The following year his government used the military to break the great shearers' strike, and he earned the nickname "Oily Sam."
Griffith was always a supporter of federation. He headed the Queensland delegation to the 1891 Melbourne Constitutional Convention, and his fine legal mind brought him a leading role in its deliberations. "It fell to my lot to draw the Constitution," he wrote, "after presiding for several days on a Committee, and endeavouring to ascertain the general consensus of opinion."
This first draft enshrined the basic pronciples of what eventually emerged as Australia's constitution: a federal system with specified powers ceded by the colonies to a national government, a bicameral legislature with an upper house in which all the colonies would have equal representation, and a federal judiciary.
In 1893 Griffith promoted himself from premier to Chief Justice of the Supreme Court of Queensland. Hewas therefore not a delegate to the 1897 conventions which produced the final draft of the Constitution, but he acted as a behind-the-scenes advisor to Sir Robert Garran, secretary of the Drafting Committee, which followed the structure he had laid out in 1891. In 1899 he (most improperly) campaigned publicly for a yes vote in the federation referendum in Queensland.
When the federal Parliament passed the Judiciary Act in 1903, creating the High Court of Australia, Griffith was the natural choice as the first Chief Justice. During his sixteen years on the bench Griffith sat on some 950 reported cases. In 1913 he visited England and sat on the Privy Council. After 1910 his health declined, and in 1917 he suffered a stroke. He retired from the Court in 1919 and died at his home in Brisbane on 9 August 1920. He is commemorated by Griffith University in Brisbane. The Samuel Griffith Society is a conservative organisation dedicated to defending what it sees as the principles of the Constitution.