In 1778 the family moved to Philadelphia, where the elder Pickering was serving as adjutant general of the Continental Army.

In May of 1783, Rebecca Pickering and her children moved back to Philadelphia due to her ill health, while her husband remained in New York.

[3] In 1797, Pickering was appointed as the secretary to the United States Minister to Portugal William Loughton Smith.

His book purchases eventually put him in debt and he was forced to sell 2,000 volumes at a public auction.

[2] At the time Pickering was still residing with his unmarried uncle, a widowed aunt, and a second cousin, Sarah White.

In 1806, Pickering was offered the position of Hancock Professor of Hebrew and other Oriental Languages at Harvard University, but declined it.

In 1814 he was considered for the newly created Eliot Professorship of Greek Literature at Harvard College, but his other duties kept him from taking the job.

The following year his A vocabulary; or, Collection of words and phrases, which have been supposed to be peculiar to the United States of America was republished by Cummings and Hilliard.

[2] In 1821, Pickering and John King were assigned to represent Stephen Merrill Clark, a 16-year-old from Newburyport, Massachusetts who was charged with arson.

Outrage at the execution of the youth resulted in the state legislature's reducing the punishment for arson to life imprisonment or any term of years in prison.