He worked in banking and manufacturing before entering politics. He was elected as a Republican to the 48th United States Congress (March 4 1883 - March 3 1885) to represent New Jersey's 3rd congressional district, but was an unsuccessful candidate for reelection in 1884.
He was elected to the 50th United States Congress (March 4, 1887 - March 3, 1889), and again was an unsuccessful candidate for reelection in 1888. He was named Chairman of the New Jersey Republican State Committee in 1891, resigning the following year to run as the Republican candidate for Governor of New Jersey. He lost the 1892 gubernatorial race to Democrat George Theodore Werts. He was a member of the committee to revise the judiciary system of New Jersey.
He was elected to the United States Senate in 1899 and reelected in 1905, serving in the Senate from March 4 1899 to March 3 1911. He was chairman of the Committee on the Geological Survey (Fifty-seventh United States Congress) and Committee to Audit and Control the Contingent Expenses (Fifty-eighth United States Congress through Sixty-first United States Congress).
Keansburg, New Jersey is named in honor of John Kean. In 1884, Kean played a key part in helping the town, at the time called Granville, to obtain its first post office. During that year, the name Keansburg was adopted.