He established a practice in Tennessee prior to the American Civil War.

In 1853, he was that party's candidate for governor, losing to Democrat Andrew Johnson by around 2250 votes.

He served in the Confederate States of America Senate from 1862 to 1865 and was widely known as the "Eagle Orator of Tennessee."

Through his personal friendship with President Davis, he was influential in the Confederate government.

Henry owned Emerald Hill, a large mansion overlooking the Cumberland River in Clarksville, Tennessee now listed in the National Register of Historic Places and serves as the alumni center for the neighboring Austin Peay State University.