Kellogg was born in Potsdam, New York on December 22, 1856. His family moved to Minnesota in 1865.
In 1880, he became a member of the masonic lodge Rochester No. 21 where he received the degrees of freemasonry on April 1, April 19, and May 3.
In 1886, Kellogg was married to Clara May Cook (1861–1942), the daughter of George Clinton Cook (1828–1901) and Elizabeth (née Burns) Cook (1838–1908).
In 1905, Kellogg joined the federal government when Theodore Roosevelt asked Kellogg to prosecute a federal antitrust case. In 1906, Kellogg was appointed special counsel to the Interstate Commerce Commission for its investigation of E. H. Harriman. In 1908, he was appointed to lead the federal prosecution against Union Pacific Railroad, under the Sherman Antitrust Act. His most important case was Standard Oil Co. of New Jersey v. United States, 221 U.S. 1 (1911). Following this successful prosecution, he was elected President of the American Bar Association (1912–1913).
In 1916, Kellogg was elected as a Republican to the United States Senate from Minnesota and served from March 4, 1917 to March 4, 1923 in the 65th, 66th, and 67th Congresses. During the ratification battle for the Treaty of Versailles, he was one of the few Republicans who supported ratification. He lost his re-election bid in 1922 and, in 1923, he was a delegate to the Fifth International Conference of American States at Santiago, Chile.
In 1924, he was appointed by President Calvin Coolidge as Ambassador Extraordinary and Plenipotentiary to Great Britain, serving from January 14, 1924 to February 10, 1925. He succeeded George Brinton McClellan Harvey who served under Warren G. Harding and was succeeded by Alanson B. Houghton so that Kellogg could assume the role of Secretary of State.
He was associate judge of the Permanent Court of International Justice from 1930 to 1935.
In 1937, he endowed the Kellogg Foundation for Education in International Relations at Carleton College, where he was a trustee. His house in St. Paul, the Frank B. Kellogg House was listed as a National Historic Landmark in 1976.
As Secretary of State, he was responsible for improving U.S.–Mexican relations and helping to resolve the long-standing Tacna–Arica controversy between Peru and Chile. His most significant accomplishment, however, was the Kellogg–Briand Pact, signed in 1928. Proposed by its other namesake, French foreign minister Aristide Briand, the treaty intended to provide for "the renunciation of war as an instrument of national policy." He was awarded the 1929 Nobel Peace Prize in recognition.