Each issue carried a subtitle of "Devoted to Every Department of Literature and the Fine Arts" or some variation thereof and included poetry, fiction, nonfiction, reviews, and historical notes.

In the inaugural issue, he stated that his aim was "to stimulate the pride and genius of the south, and awaken from its long slumber the literary exertion of this portion of our country.

We say this not in a reproachful spirit, but in a somewhat sad conviction of mind, that we who live on the sunny side of Mason and Dixon's line are not yet sufficiently inspired with a sense of importance of maintaining our just rights, or rather our proper representation in the Republic of Letters.In February 1861, the Southern Literary Messenger defended the secession movement by publishing an article by William H. Holcombe, a doctor, entitled "The Alternative: A Separate Nationality, or the Africanization of the South."

Edgar Allan Poe was hired as a staff writer and critic in August 1835, possibly based on a recommendation to White from John Pendleton Kennedy.

Besides criticism, Poe published many first printings of his now famous works in the Messenger, including the controversial "Berenice", "Morella" and, in installments, parts of his only novel The Narrative of Arthur Gordon Pym of Nantucket.