He is also known as the foster father (and subsequently father-in-law) of famous American Civil War general William Tecumseh Sherman.

He resigned on September 11, 1841, along with the entire cabinet (except Secretary of State Daniel Webster), in protest of Tyler's veto of the Banking Act.

As James G. Blaine later wrote: Thomas Ewing of Ohio, selected to organize the Department of the Interior, just then authorized by law, was a man of intellectual power, a lawyer of the first rank, possessing a stainless character, great moral courage, unbending will, an incisive style, both with tongue and pen, and a breadth of reading and wealth of information never surpassed by any public man in America.

Ewing initiated the Interior Department's culture of corruption by wholesale replacement of officials with political patronage.

In 1850, Ewing was appointed to the Senate to fill the vacancy created by the resignation of Thomas Corwin, and served from July 20, 1850 – March 3, 1851.

In 1861, Ewing served as one of Ohio's delegates to the peace conference held in Washington in hopes of staving off civil war.

Ewing married Maria Wills Boyle, a Roman Catholic, and raised their children in her faith.