On February 14, 1859, Oregon entered the Union as the 33rd state.
In 1860, the Oregon Legislative Assembly elected Nesmith to the United States Senate.
A Democrat, he served from March 4, 1861, to March 4, 1867, and was an unsuccessful candidate for re-election.
While in the Senate, he and Reverdy Johnson were the only Democrats in that chamber to vote for the Thirteenth Amendment to the United States Constitution to abolish slavery.
After serving in the Senate, he was appointed Minister to Austria, but his nomination was not confirmed.

After returning to Rickreall, he served as road supervisor of Polk County in 1868.
Nesmith was elected to the Forty-third Congress to fill the vacancy caused by the death of his cousin, Joseph G. Wilson, and served from December 1, 1873, to March 3, 1875.
He did not seek re-nomination in 1874 to the Forty-fourth Congress and returned to farming in Polk County.
On February 14, 1859, Oregon entered the Union as the 33rd state. In 1860, the Oregon Legislative Assembly elected Nesmith to the United States Senate. A Democrat, he served from March 4, 1861, to March 4, 1867, and was an unsuccessful candidate for re-election. While in the Senate, he and Reverdy Johnson were the only Democrats in that chamber to vote for the Thirteenth Amendment to the United States Constitution to abolish slavery. After serving in the Senate, he was appointed Minister to Austria, but his nomination was not confirmed.
After returning to Rickreall, he served as road supervisor of Polk County in 1868. Nesmith was elected to the Forty-third Congress to fill the vacancy caused by the death of his cousin, Joseph G. Wilson, and served from December 1, 1873, to March 3, 1875. He did not seek re-nomination in 1874 to the Forty-fourth Congress and returned to farming in Polk County.
James Nesmith