He was the Democratic candidate for the U.S. House seat held by Schuyler Colfax in 1862, losing only narrowly.

[1] Shortly thereafter, Turpie was elected to the United States Senate from Indiana to fill the unexpired term of Jesse D. Bright who had been expelled for alleged disloyalty.

He served for just under two months, until the regularly elected senator, Thomas A. Hendricks, arrived to take his seat.

His return to the U.S. Senate, after 24 years and 1 day out of office, marks the third longest gap in service to the chamber in history.

Journalist and historian Claude G. Bowers, while acknowledging Turpie's reputation as a scholarly speaker of "classic English" and a scrupulous upholder of senatorial decorum, also recorded an anecdote reflecting the dry mischief of which Turpie was capable:[W]hen Henry Cabot Lodge entered the Senate a bit pretentiously and his colleagues thought a bit of hazing might cut him down to size, Turpie, a master of satire, had been assigned the task, because he could do it so beautifully.