In 1840, he actively campaigned for the Whig candidate, William Henry Harrison, and gained for himself a national reputation as a stump orator under the name of the "Old Salt Boiler." Upon Harrison's inauguration in 1841, he was rewarded with a cabinet post as Secretary of the Treasury. He served in this capacity from March 5 to September 13, 1841. In addition to being entrusted with a distribution of a good deal of the patronage available to the Administration, he investigated and reorganized the New York Custom House, he saw to the expenditure of public funds for the care of disabled seamen, he supervised the investment of the funds left to the United States by Joseph Smithson of London for the establishment at Washington of an institution "for the increase and diffusion of knowledge among men" -- the origin of the Smithsonian Institute -- and he had a hand in the settlement of the McLeod affair, which grew out of a disturbance on the Canadian-American Border. In his first official report he proposed measures designed to diminish the national debt, he attacked the Independent Treasury Act which had been passed the previous year, and he advocated the establishment of a National Bank. Indeed, the chartering of a National Bank was his paramount concern. He played a major role in drafting two bills that would have chartered such a bank. However, both were vetoed by Tyler who had succeeded to the Presidency upon Harrison's untimely death. As a result of the second veto, Ewing submitted a scathing letter of resignation and, on September 13, 1841, he left the cabinet and entered into a law partnership with his oldest son, Philemon Beecher Ewing.

In 1844 he campaigned vigorously for Henry Clay's election to the Presidency. Although the Whigs carried the Ohio Legislature in that year -- the only time they were able to do so when a Senator was to be elected -- and Ewing hoped to return to the Senate, he was passed over and Thomas Corwin, who had become the idol of the Ohio Whigs by agreeing to sacrifice himself as candidate for governor in 1840, was chosen instead. By 1848, there were indications that Ewing was angling for the vice-presidential nomination. Although favored by the Taylor forces at the convention, his name was withdrawn, without either his assent or knowledge, by a fellow Ohioan, Lewis D. Campbell, who, chagrined at the failure of Henry Clay to secure the nomination for President, insisted that Ohio wanted no "sugar plums." The subsequent death of Taylor in office and succession of the Vice-President made this unauthorized withdrawal of Ewing's name especially significant. But for it, Ewing, instead of Fillmore, might have been our thirteenth President.

In the subsequent campaign he actively entered the lists for Taylor. Urged to accept a cabinet position upon Taylor's victory, he would not commit himself so long as there remained a chance for the Senate. However, the "Free Soil" Whigs of Ohio, who had resented his campaigning for Taylor, a slaveholder, refused to agree to his selection as Senator. Salmon P. Chase was chosen instead. At first considered seriously for the Post Office Department, he was eventually given the newly establish Department of the Interior. A man with organizational ability was needed and Ewing had demonstrated during his term in the Senate, at which time he had written laws reorganizing the Post Office Department and the General Land Office, that he was such a man. He served from March 8, 1849, to July 23, 1850.

However, his withdrawal from the Cabinet did not result in his immediate retirement from public life. When Thomas Cerwin became Secretary of the Treasury, Ewing was appointed by Governor Seabury Ford of Ohio to fill out Cerwin's unexpired term in the Senate. Thus, once again, Ewing found himself in the forum he loved so much. During this brief term he served on the Finance Committee, he opposed the Fugitive Slave Law and Clay's Great Compromise, and he advocated the establishment of a branch mint in California, a reduction in the postal rates, internal improvements, and various other measures of public importance. As the term was drawing to a close in 1851, he was defeated in a bid for re-election, once again because of the opposition of the "Free Soil" Whigs in the Ohio Legislature. With this defeat, he retired once again to private life and the practice of law. Although he thereafter maintained his interest in public affairs, he never again held public office.

During the last twenty years of his life, he spent his winters in Washington, arguing his cases -- his particular forte was Real Estate Cases -- before the Supreme Court, and the rest of the year, generally, at home in Lancaster, Ohio. In 1856, he refused to support any of the candidates for the Presidency. In 1860, although he preferred John Bell, the nominee of the Constitutional Union Party, he nevertheless supported Abraham Lincoln, a former Whig and political friend, because he felt that in Ohio only Lincoln could defeat Stephen A. Douglas whom he regarded as too reckless. He also felt that the Republican Party, in espousing the Tariff and other old Whig principles, had veered to a more conservative course than it had adopted originally. He did, however, take exception