In January 1875, Kernan was elected a U.S. Senator from New York, the first Catholic senator from New York and its first Democratic senator in 24 years. He served from March 4, 1875 to March 3, 1881, alongside Roscoe Conkling. He numbered among his friends Abraham Lincoln, Horatio Seymour, Samuel J. Tilden, Thomas F. Bayard, Grover Cleveland, and other distinguished Americans, and his counsel and advice were often sought by them. He showed so decided a spirit of justice and moderation that he was often consulted by President Lincoln on matters pertaining to the conduct of the war.