[1] Born in Salem in the Province of Massachusetts Bay, Pickering began a legal career after graduating from Harvard College.

After the war, Pickering moved to the Wyoming Valley of Pennsylvania and took part in the then colony's 1787 ratifying convention for the United States Constitution.

Pickering won election to represent Massachusetts in the United States Senate in 1803, becoming an ardent opponent of the Embargo Act of 1807.

He was one of nine children and the younger brother of John Pickering (not to be confused with the New Hampshire judge) who would eventually serve as Speaker of the Massachusetts House of Representatives.

Salem minister William Bentley noted on Pickering: "From his youth his townsmen proclaim him assuming, turbulent, & headstrong.

"[4] After graduating from Harvard, Pickering returned to Salem where he began working for John Higginson, the town clerk and Essex County register of deeds.

"[6] The manual was used as the Continental Army drill book until replaced by Baron von Steuben's Regulations for the Order and Discipline of the Troops of the United States[7] On February 26, 1775, men under Pickering's command were involved in one of the earliest military engagements in the American Revolution, a confrontation locally referred to as "Leslie's Retreat."

Leslie's men were thwarted from crossing the North River bridge and searching the outlying farms by Pickering's militia and citizens of Salem.

Thomas Barnard Jr. of the North Church famously left his pulpit that morning to meet the British troops at the bridge.

Two months later, Pickering's troops marched to take part in the Battles of Lexington and Concord but arrived too late to play a major role.

The chain blocked the Royal Navy from proceeding up the Hudson River past West Point and protected that important fort from attack for the duration of the conflict.

When he attempted to settle a controversy generated by John Armstrong who was antagonizing Connecticut settlers living in the area, Pickering was captured and held hostage for nineteen days.

As Secretary of State he is most remembered for his strong Federalist Party attachments to British causes, even willingness to wage war with France in service of these causes during the Adams administration.

Pickering opposed the American seizure and annexation of Spanish West Florida in 1810, which he believed was both unconstitutional and an act of aggression against a friendly power.

[15] He held several conferences with the special British envoy George Rose and proposed the creation of a pro-British party in New England and urged Rose to persuade British Foreign Secretary George Canning to maintain his hard line against America with the hopes that Jefferson would resort to even more extreme measures, which would ultimately effect a political suicide for the Republicans.

Pickering also published his open letter to the Massachusetts Republican governor, which he refused even to read; it contained harsh criticism of the Embargo Act, claimed that Jefferson had presented no real arguments for its enactment, and called for its nullification by the state legislators.