As editor of the Philadelphia Aurora, Duane became a leading publicist for Thomas Jefferson's Democratic-Republican opposition as well as for a community United Irish émigrés with whom he protested the Alien and Sedition Acts.

In his later years, Duane joined war hero Andrew Jackson and the Democratic Party in their opposition to concentrating control of public credit in a central bank.

He found employment, apprenticing as a printer with a local paper, the Hibernian Advertiser, that supported the Volunteer movement for reform, and celebrated the American struggle for independence.

[7][4]: 117–118 [3]: 20 The East India Company authorities were alarmed by his reporting of news from revolutionary France, and of intrigues in the various Indian princely courts where a return of French influence was greatly feared.

Invited to breakfast by the Governor-General, Lord Teignmouth, he was seized on the way by Sepoys, held in the dungeon (the "Black Hole") of Fort William, and placed a ship bound for England.

[4]: 121–122 Through the period 1795-96, Duane took an active role in the LCS,[4]: 121–122  and may have followed a number of prominent Irish members—Colonel Edward Despard (who had returned from the West Indies equally disillusioned by Britain's colonial mission)[10] the brothers Benjamin and John Binns, Arthur O'Connor, and William Henry Hamilton[11]—in taking the Test or pledge of the United Irishmen.

Before the government of William Pitt, charging collusion with the United Irishmen and with the French, proscribed the Society, with John Binns,[12] Duane chaired the last, and grandest, of its mass meetings.

Speaking alongside veteran reformers Joseph Priestley, Charles James Fox, and John Thelwall, crowds estimated at upwards of 200,000 heard Duane confirm his Painite commitment to natural rights and democratic liberties.

[4]: 122  Three days later, George III, in procession to the state Opening of Parliament, had the windows of his carriage smashed by crowd shouting "No King, No Pitt, No war".

[16][17] As a result of his attempt to justify the French position in the XYZ Affair, Bache faced charges of seditious libel against President John Adams and his Federalist administration.

[20] He directed the same invective against Duane's growing circle of United Irish émigrés,[21] describing them as men "animated by the same infamous principles, and actuated by that same thirst for blood and plunder, which had reduced France to a vast human slaughter-house".

[21]: 92  In December 1798, in an editorial reprinted by Cobbett, the leading Federalist paper, the Gazette of the United States, identified Duane as one of the society's principals, alongside his Market Street neighbor, the publisher Matthew Carey, and, James Reynolds.

[25] A United Irish veteran from Tyrone,[26] Reynolds had co-authored with Duane The Plea of Erin, a memorial presented to Congress protesting the Alien and Sedition Acts.

In February 1799, juries rejected attempts to prosecute Duane and Reynolds for sedition following an incident, reported by the Federalists as a "United Irish riot".

[21]: 107–111  He was again charged, for seditious libel in response to articles published in the Aurora intimating that Great Britain had used intrigue to exert its influence on the United States.

But able to produce a letter that John Adams himself had written a few years earlier implying the same in respect of the appointment of Thomas Pinckney as the United States' minister to London, Duane avoided prosecution.

[29] In May 1799, Duane was severely beaten in his home by army officers demanding to know the source for an article detailing abuses in the repression of Fries's Rebellion in western Pennsylvania.

In addition to protecting Duane and his presses from further attack, ultra-Republicans saw the drilled and armed volunteers as a counter to the perceived threat of a Federalist standing army.

In the Aurora, he published details of the Ross Bill which would have established a closed-door Grand Committee, chaired by the Chief Justice of the Supreme Court, an Adams appointee, with powers to disqualify College electors.

Stung by the President's seeming ingratitude, James Callender, who had been fined and imprisoned under the Sedition Act for his scurrilous attacks on Adams, attempted, in effect, to blackmail Jefferson.

In the next issue of his Richmond Recorder, under the heading "The President Again," Callender wrote that it was "well known that the man, whom it delighteth the people to honor, keeps, and for many years past has kept, as his concubine, one of his own slaves.

[3]: 36–39 During the war, Duane wrote a letter to Jefferson on 11 August 1814, expressing alarm at Britain's policy of recruiting fugitive American slaves into the British military.

[21]: 189 Although prominent United Irish exiles, such as Thomas Addis Emmet and William Sampson, continued as uncompromising abolitionists, many of their compatriots were to follow Duane in conforming to racist, pro-slavery sentiment.

[44] He published and promoted Sampson against the Philistines, or, The reformation of lawsuits, by Jesse Higgins, in which the alternative of a general codified law of reference is presented as "justice made cheap, speedy, and brought home to every man's door".

[48] A result of Duane's disappointment was a bitter print war with his former associate in the London Corresponding Society, John Binns, Snyder's trusted advisor and, from 1807, editor in Philadelphia of the Democratic Press.