He devoted himself early to the cause of colonial rights and popular liberty, joined the associated Sons of Liberty, in whose discussions he took a leading part, and became an active Whig. In 1769 he was counsel in the famous Lechmere slave case. In 1773 he was associated with John Adams in the prosecution in behalf of the Rhode Island patriots in the matter of the Rome and Moffatt letters. When Governor Hutchinson sailed on I June 1774, the Boston bar sent an address to the retiring governor, which Dana, though one of the youngest of them, opposed with vigor. In September 1774, he was the delegate from Cambridge to the 1st provincial congress of Massachusetts. In the beginning of April 1775, he sailed for England (where his brother Edmund was settled as a minister at Wroxeter), bearing confidential letters on the critical state of colonial feeling from Josiah Quincy, Joseph Warren, Dr. Samuel Cooper, and other patriots. Through his brother, who was allied by marriage with the Kinnaird and Pulteney families, he came in contact with persons of political influence in England, and in April 1776, after his return, he informed Washington that there was no reason to expect peace from Britain. While in England he became acquainted with Dr. Richard Price, and furnished him with information, which he embodied in his work in defense of the colonies (London, 1776). In May 1776, the Massachusetts assembly chose him a member of the executive council, which united executive with legislative functions, and was re-elected annually until 1780. In November 1776, he was chosen a delegate from Massachusetts to the continental congress, and took part in framing the articles of confederation, and was again sent to the congress of 1778, and made chairman of the committee charged with the reorganization of the army. He remained in the camp at Valley Forge with Joseph Reed, Governor Morris, and other members of the committee from January till April 1778, and, in consultation with General Washington, drew up the plan of annual drafts that was submitted to congress, and returned to the commander-in-chief on 4 June with directions that he should proceed with it, with the advice and assistance of Messrs. Reed and Dana, or either of them. He served with Governor Morris and William H. Drayton on the committee to which Lord North's conciliatory bills were referred in 1778, on whose report these overtures were unanimously rejected, and the intended effect of the peace commission frustrated.

Governor Johnstone, with whom he had become acquainted in England, was one of the commissions, and wrote to him in the hope of securing his co-operation. This letter, with others received by Reed and Robert Morris, was transmitted to congress on 18 July. On 29 September 1779, Mr. Dana was appointed secretary to the embassy of John Adams, who was appointed commissioner to negotiate treaties of peace and commerce with Great Britain. He sailed with Mr. Adams, on 13 November 1779, in the French frigate "Sensible." They landed at Ferrol, Spain, and reached Paris 9 February 1780. When Adams, in consequence of a diplomatic quarrel with Vergennes, left Paris for Amsterdam on 27 July. Dana remained in Paris until the commission of congress (to Mr. Adams. and eventually to himself, to raise loans in Europe) reached him on 12 September He then joined A(lams in Amsterdam, and remained with him till December. Returning to Paris, he received, on 15 March 1781, a commission from congress as minister to the court of St. Petersburg, having been appointed to that post on 18 December 1780. He remained with Mr. Adams in Holland from April till 7 July when he left for St. Petersburg, journeying by way of Frankfort and Berlin. He resided at the Russian court two years, where he had frequent and friendly communications with Count Ostermann, the foreign minister, but was unable to secure the recognition of the independence of the United States. When. even after the signature of the preliminaries of peace, the government of the Empress Catherine still refused to receive him as an accredited minister of an independent and friendly power, he asked for his leave from congress, and departed from St. Petersburg on 4 September 1783, sailing direct to Boston, where he arrived in December.

In February 1784, he was elected by the assembly a delegate to the continental congress, took his seat on 24 May and was appointed to represent Massachusetts on the committee of the states, which was vested with some of the powers of congress during" the recess, and continued in session till 11 Aug'. On 18 January 1785, Governor Hancock appointed him a justice of the Supreme Court of Massachusetts. On 29 August 1786, ha was elected a delegate to the Annapolis convention, which fixed the time and place for the Federal convention of 1787 that adopted the constitution of the United States. He was also elected a delegate to this body on 9 April 1787, but was prevented from attending by his judicial duties and the state of his health, which had been impaired by his residence in St. Petersburg. He was chosen a member of the Massachusetts state convention that met in January 1788, to ratify the Federal constitution. In that body, on whose decision depended the fate of the Federal constitution, a majority of the members were at first opposed to the new form of government. Judge Dana labored to secure the ratification of the constitution with John Hancock, Theophilus Parsons, and others, and aided in obtaining a majority for its adoption on 6 February 1788. On 29 November 1791, after the death of Judge Sargent, he was appointed chief justice of Massachusetts, and held that office for fifteen years, during which he took no part in political affairs, except as a presidential elector in 1792 and 1800. On 5 June 1797, President Adams appointed him a special envoy to the French republic, with Cotesworth Pinckney and John Marshall; but he was compelled, by the precarious state of his health, to decline the office, which was then given to Elbridge Gerry. He retired from the bench in 1806, and was succeeded by his friend, Theophilus Parsons. He vigorously opposed Jefferson's embargo in public speeches at Cambridge, but seldom took part after that in public discussions. He was one of the founders of the American academy of arts and sciences, and interested himself in enterprises for the benefit of the neighborhood of Boston. After his retirement the old leaders of the Federal party who had been his associates in political life, and entertained the younger literary society of Cambridge frequently visited him at his house.

Judge Dana possessed a large fortune, chiefly in lands. He was a typical representative of the Federal gentry of New England, who looked upon themselves as the guardians of the people, and sought to preserve distinctions of birth and station. He possessed a high sense of honor and of public duty, was ardent and passionate in temperament, intolerant of timid or temporizing measures, of an active and energetic character, remarkable for his nervous and impressive eloquence, an acute and learned jurist, and an austere and dignified magistrate.