Hergesheimer was born in Philadelphia and initially studied as a painter but quickly turned to writing. He established an early reputation with his first novel The Lay Anthony in 1914. Three Black Pennys, which followed in 1917, chronicled the fictional lives of three generations of Pennsylvania ironmasters and cemented the author's style of dealing with upperclass characters through a floridly descriptive style he referred to as "aestheticism." Hergesheimer also received critical recognition for his novels Java Head (1919), Linda Condon (1919), and Balisand (1924).

Hergesheimer's reputation fluctuated wildly in his own lifetime, from a peak of acclaim and popularity in the 1920s to almost total obscurity by the time of his death. Java Head, a miscegenation story told from multiple viewpoints that is generally considered his best novel, was a considerable popular success, and his flamboyant, ornate, highly descriptive style (which can be seen to best effect in works like the travelogue San Cristobal de la Habana) was considered elegant and powerful. Hergesheimer's manner of writing, known at the time as the "aesthetic" school, remained in demand throughout the 1920s (with F. Scott Fitzgerald's The Great Gatsby being the most durable example of a book written in this style). Sinclair Lewis's novel Babbitt includes an extensive passage in which the title character reads from Three Black Pennies. A 1922 poll of critics in Literary Digest voted Hergesheimer the "most important American writer" working at the time. Hergesheimer's works of long-form and short fiction sold well with both male and female readerships; a 1929 teaser in for an upcoming serialized story in Cosmopolitan, for example, called Hergesheimer a writer "who understands women better than any writer alive today."

Tastes changed decisively in the 1930s, however, with both critics and writers favoring a more terse, tough-guy style. Hergesheimer's gift for flowery writing did not translate well in this new environment, and by the middle of the decade his popularity had fizzled. His last novel The Foolscap Rose, appeared in 1934. H.L. Mencken's diary describes Hergesheimer's frustration at the decline of his popularity and the lack of interest by his publishers, and according to one literary legend, when Hergesheimer asked why nobody was interested in his books anymore, Mencken replied, "I don't know, Joe. I'll always enjoy watching you swing from tree to tree."

Hergesheimer's reputation has not recovered from this low point, although he still has some champions. The weakness in his method can be seen in books like Cytherea, wherein the author's aesthetic concerns overwhelm all other aspects of the writing, resulting in thin plot and characterization and a certain precious quality in the descriptions. Indeed, Clifton Fadiman considered his novels to be "deficient in mere brain-power". On the other hand, his descriptive writing occasionally holds great power. When asked in 1962 what was his favourite American novel, Samuel Beckett replied 'one of the best I ever read was Hergesheimer's Java Head'.

His short story "Tol'able David" was made into a highly successful and acclaimed 1921 silent film. Other notable film adaptations include Java Head (US, 1923), Wild Oranges (1924), and Cytherea (1924), and Java Head (UK, 1934). Eight films and one television special were adapted from Hergesheimer's work.

Hergesheimer died in Sea Isle City, New Jersey. He is buried at Oaklands Cemetery in West Chester, Pennsylvania next to his wife Dorothy (1884-1969).

Novels

• The Lay Anthony (Mitchell Kennerley, 1914; Alfred A. Knopf, 1919)
• Mountain Blood (Kennerley, 1915; Knopf, 1919)
• The Three Black Pennys (Knopf, 1917)
• Java Head (Knopf, 1919)
• Linda Condon (Knopf, 1919)
• Cytherea (Knopf, 1922)
• The Bright Shawl (Knopf, 1922)
• The Presbyterian Child (Knopf, 1923)
• Balisand (Knopf, 1924)
• Tampico (Knopf, 1926)
• swords and roses(Knopf, 1928,1929 from copyright date)
• The Party Dress (Knopf, 1930)
• Berlin (Knopf, 1931)
• The Foolscap Rose (Knopf, 1934)

Short stories

• Gold and Iron (Knopf, 1918) (Contains three novellas: Wild Oranges, Tubal Cain, and The Dark Fleece.)
• The Happy End (Knopf, 1919)
• Tol'able David
• Wild Oranges (Knopf, 1922)
• Tubal Cain (Knopf, 1922)
• The Dark Fleece (Knopf, 1922)
• Quiet Cities (Knopf, 1928)
• Tropical Winter (Knopf, 1933)

Belles-Lettres

• San Cristobal de la Habana (Knopf, 1920)
• From an Old House (Knopf, 1925) limited, signed edition, out of print
• Swords & Roses (Knopf, 1929)