In 1817, 22-year old James Harper and his 20-year old brother, John, set up a small printing firm in New York City called J. & J. Harper. Joined later by their younger brothers, Joseph Wesley and Fletcher, the firm became the largest book publisher in the United States by 1825. The name was changed to Harper & Brothers in 1833, and survives today as Harper-Collins.

Under Fletcher's guidance, the firm started Harper's Monthly in June 1850. The first managing editor was Henry Raymond, who soon went on to found and published The New York Times. Harper's Monthly became, and still is, an outstanding literary magazine.

Motivated by the success of Frank Leslie's Illustrated Weekly which was started a year earlier, Fletcher Harper published the first issue of Harper's Weekly on January 3, 1857. Harper's was aimed at the middle and upper socio-economic classes, and tried not to print anything that it considered unfit for the entire family to read. In addition to the importance of illustrations and cartoons by artists like Winslow Homer and Thomas Nast, the paper's editorials played a significant role in shaping and reflecting public opinion from the start of the Civil War to the end of the century. George William Curtis, who was editor from 1863 until his death in 1892, was its most important editorial writer.

From its founding in 1857 until the Civil War broke out in April 1861, the publication took a moderate editorial stance on slavery and related volatile issues of the day. It had substantial readership in the South, and wanted to preserve the Union at all costs. Some critics called it "Harper's Weakly."

Harper's Weekly would have preferred William Seward or possibly Stephen Douglas for president in 1860, and was lukewarm towards Lincoln early in his administration. When war came, however, its editorials embraced Lincoln, preservation of the Union, and the Republican Party. Military coverage became paramount in every issue, as its news and illustrations kept soldiers at the various fronts and their loved ones at home up to date on the details of the fighting.

The following quotation from the April 1865 issue of the North American Review shows how a leading peer publication viewed the wartime contributions of Harper's Weekly.

"Its vast circulation, deservedly secured and maintained by the excellence and variety of its illustrations of the scenes and events of the war, as well as by the spirit and tone of its editorials, has carried it far and wide. It has been read in city parlors, in the log hut of the pioneer, by every camp-fire of our armies, in the wards of our hospitals, in the trenches before Petersburg, and in the ruins of Charleston; and wherever it has gone, it has kindled a warmer glow of patriotism. It has nerved the hearts and strengthened the arms of the people, and it has done its full part in the furtherance of the great cause of the Union, Freedom, and the Law."

After the war, Harper's Weekly continued to be a major factor in Ulysses Grant's presidential victories in 1868 and 1872, the overthrow of New York City political boss William Tweed in 1871, and the first election of Grover Cleveland in 1884. Its circulation exceeded 100,000, peaking at 300,000 on occasion, while readership probably exceeded half a million people.

Harper's Weekly continued on until May 1913, surviving a bankruptcy at the turn of the century through the financial kindness of J. P. Morgan. In 1913, it changed ownership, adopted a leftist political stance, and finally gave up the ghost by selling its subscription list to The Independent in 1916.