Relatives assisted him in obtaining a position in the customs service as deputy collector, or comptroller, of the port of Edenton, North Carolina.

The grandson of a clergyman, he was a devout Anglican throughout his life and his writings display an interest in spirituality and metaphysics beyond a simple attachment to organized religion.

In 1774, he wrote To the Inhabitants of Great Britain where he laid out arguments opposing the concept of parliamentary supremacy over America.

Iredell was the floor leader for the Federalists (North Carolina later ratified the Constitution after Congress amended it through the addition of the Bill of Rights).

In the unanimous decision in Calder, the Court held that the Clause applied to criminal cases only, deciding that the legislature's act was not unconstitutional.

He stated, "The principles of natural justice are regulated by no fixed standard; the ablest and the purest men have differed upon the subject; and all the court could properly say, in such an event, would be, that the legislature (possessed of an equal right of opinion) had passed an act which, in the opinion of the judges, was inconsistent with the abstract principles of natural justice."

[4] Justice Iredell's opinion in Calder helped establish the principle of judicial review five years before it was tested in Marbury v. Madison (1803).

Iredell's charge to the federal grand jury in Fries' Case is commonly cited as evidence that the framers' intent was to limit the scope of the First Amendment to freedom from prior restraint.

Partially due to the heavy burden of travel, Justice Iredell's health failed and he died suddenly on October 20, 1799, in Edenton, North Carolina, at the age of 48.

Iredell mirrored contemporaries like Thomas Jefferson and George Washington in openly condemning slavery while participating in the practice itself.

[6][7] In 1769, Iredell assisted his father, Thomas, in selling a runaway slave and requested herring and red-oak staves as part of the proceeds.

Iredell believed that the Constitution would not be ratified by South Carolina nor Georgia without the inclusion of the Slave Trade Clause, writing, "Our situation...makes it necessary to bear the evil as it is.

'"[10][5] In the time between ratification of the Constitution and abolition, Iredell wrote, "judgement upon slavery in the United States must rest between the individuals' consciences and God.

[11][12] During his lifetime, James Iredell freed some of his slaves, including Peter, Edy, and Dundee, and visited them in subsequent years in Philadelphia.