He served in the United States House of Representatives and Senate before becoming Secretary of the Treasury under President Abraham Lincoln during the American Civil War.

A lawyer, he was a leading antislavery Whig in Maine; in Congress, he fought the Slave Power, plantation owners who controlled Southern states.

He refused nominations to Congress in 1831 and in 1838, and served in the Maine legislature again in 1840, becoming chairman of the house committee to revise the statutes of the state.

He acquired a national reputation as a lawyer and an anti-slavery Whig,[6] and in 1849 prosecuted before the United States Supreme Court an appeal from an adverse decision of Judge Joseph Story, and gained a reversal by an argument which Daniel Webster pronounced the best he had heard in twenty years.

As chairman of the finance committee, Fessenden prepared and carried through the senate all measures relating to revenue, taxation, and appropriations, and, as declared by Charles Sumner, was "in the financial field all that our best generals were in arms.

"[citation needed] President Abraham Lincoln appointed Fessenden United States Secretary of the Treasury upon Salmon P. Chase's resignation.

He declared that no more currency should be issued, and, making an appeal to the people, he prepared and put upon the market the seven-thirty loan, which proved a triumphant success, and raised $400,000,000.

[6] This loan was in the form of bonds bearing interest at the rate of 7.30%, which were issued in denominations as low as $50 so that people of moderate means could take them.

The financial situation becoming favorable on the raising of another large loan, in accordance with his expressed intention, he resigned the secretaryship, leaving on March 3, 1865, to return to the Senate, to which he had now for the third time been elected, and where he would serve for the rest of his life.

[citation needed] From 1865 to 1867, he headed the Joint Committee on Reconstruction, which was responsible for overseeing the readmission of states from the former Confederacy into the Union.

[citation needed] During President Andrew Johnson's impeachment trial in 1868, Fessenden broke party ranks, along with six other Republican senators, and voted for acquittal.

He, Joseph S. Fowler, James W. Grimes, John B. Henderson, Lyman Trumbull, Peter G. Van Winkle,[citation needed] and Edmund G. Ross[7] defied their party and public opinion and voted against conviction.

After the trial, Congressman Benjamin Butler of Massachusetts conducted hearings on the widespread reports that Republican senators had been bribed to vote for Johnson's acquittal.

In Butler's hearings, and in subsequent inquiries, there was increasing evidence that some acquittal votes were acquired by promises of patronage jobs and cash cards.

In 1867, Radical Republican senator Charles Sumner introduced legislation that would expand Reconstruction efforts that included the provision of homesteads to freedmen.

"[12] During the 1868 United States presidential election, Fessenden joined the other six pro-Johnson Republican senators in campaigning for Ulysses S. Grant,[3] who defeated Democratic nominee Horatio Seymour.

A fourth son, William Howard Fessenden, stayed in Maine to take care of the law practice his father had established.