Bird was born in New Castle, Delaware on February 10, 1806. After attending the New Castle Academy and Germantown Academy, he graduated from the University of Pennsylvania in 1824. He began to write fiction during his time in medical school and by 1827 had published in the Philadelphia Monthly Magazine. After graduating from medical school, Bird attempted to begin a medical practice but became discouraged after one year and left medicine to pursue a literary career.

In 1828, Bird's play Pelopidas won a $1000 prize offered by the actor Edwin Forrest, but was never produced. Instead, Bird wrote another play for Forrest, The Gladiator, which was produced in 1831. Bird wrote several other plays for Forrest. Forrest had promised to pay Bird more for these plays if they proved successful. Though they were, Forrest refused to give Bird additional money; Bird's frustration with Forrest pushed him into writing novels. These include Calavar (1834), The Infidel (1835), The Hawks of Hawk-Hollow (1835), Sheppard Lee (1836), Nick of the Woods (1837), and The Adventures of Robin Day (1839).

Bird also pursued a number of other interests. In 1837, he began a career as a journalist, working as the Associate Editor for The American Monthly Magazine. He became the editor of the North American Magazine and United States Gazette in 1847. He also taught medicine at the Pennsylvania Medical College and ran for Congress in 1842 (an attempt which was later aborted).

According to Christopher Looby, "Bird's biographers say that the intensity of these literary labors led to a breakdown of his health, possibly including a mental disorder, and that he retired to a farm on the Eastern Shore of Maryland in 1840 to restore himself."