Boston: In the aftermath of the Boston Massacre – a deadly street confrontation between American colonists and an occupying British brigade – John Adams, a farmer/lawyer who has moved his family into Boston to establish his legal career, takes an unpopular stand by agreeing to serve as defense attorney for the accused British soldiers. Counseled in his advocacy by his beloved wife Abigail, Adams wins the case – but surprises his friend, the Attorney General, by turning down a lucrative position with the Crown. As pro-independent sentiment boils over in Massachusetts following the Coercive/Intolerable Acts, Adams is invited to join the newly created Continental Congress. After a rousing speech to his constituents, he says an emotional goodbye to his family before heading to Philadelphia – and an uncertain future.

Following a fruitless session of the Continental Congress, a sabbatical at Adams' Braintree farm is disrupted by news of the attack on Lexington and Concord. Adams witnesses the aftermath of the bloody battle, and later reports back to Philadelphia. There, he jousts with delegates debating the pros and cons of independence, eschewing an olive-branch proposal from Pennsylvania's John Dickinson and throwing down the gauntlet for independence. As more violence rages in and around Boston, Adams nominates George Washington to lead the newly created Continental Army. After another brief return home, Adams returns to Philadelphia – and a proclamation from King George III that treason will be met with death. After several debates and postponements, Adams seconds a resolution for independence proposed by Virginia's Richard Henry Lee, and persuades Thomas Jefferson to draft a declaration. With the support of Benjamin Franklin, Adams wins over skeptical delegates, in particular, South Carolina's Edward Rutledge and convinces opponents like Dickinson to step out of the path to independence. On July 2, 1776, a final vote confirms the Congress' near-unanimous decision – New York abstained – to declare independence from England. On July 4, 1776, a document drafted by Thomas Jefferson and affirming that declaration is adopted by the Congress. While Abigail tends to an outbreak of smallpox in Massachusetts, the Declaration of Independence is read to a raucous crowd in Philadelphia. Adams writes to his wife, "The break is made, and now our work begins."

A new period of separation from Abigail looms when Adams is appointed Minister Plenipotentiary to France along with Benjamin Franklin. Their mission is to secure French financial and military support for America's Revolutionary War effort. Abigail insists that Adams take along their son, John Quincy. The two endure a rough ocean voyage – and a skirmish with a British warship – in making their way to France. Their arduous journey includes the deaths of several seamen and impresses upon Adams the human costs of war. Once John and John Quincy arrive in France, the difference in styles between Adams and Franklin, the relaxed libertine, become apparent. As Abigail dines with a French Admiral in her husband's stead back home, Adams endures a series of uncomfortable encounters in Paris. His strident demands that France increase their naval commitment to America's war effort upsets the French diplomats and draws the wrath of Franklin, whose credo is that a good diplomat "can accomplish much by appearing to accomplish little." Vexed after learning Franklin has been appointed sole minister to France, Adams heads to Holland to solicit funds, with little initial success. After sending John Quincy to Russia to serve as secretary to the American envoy there, Adams falls victim to a long illness and fever, helpless to further advance the revolution he helped spawn.

Convalescing in Holland, Adams learns of the British surrender to Washington at Yorktown. The Dutch, unwilling to part with their money during the war, now generously open their pockets to Adams and America. Returning to France to secure commerce with other nations, Adams sends for Abigail, and the two reunite in his opulent mansion in Paris. Also arriving is Jefferson, who suffered a catastrophic loss with the death of his wife. Both Jefferson and Abigail fall under Paris' heady spell, attending opera and luxuriating in the city's intoxicating lifestyle. But a missive from America sends Adams to London as the nation's first minister to Britain, while Jefferson replaces Franklin in Paris. In London, Adams has a dramatic and memorable meeting with King George III, in which the King recognizes the friendship of the United States as an independent nation. With a new federal government about to be elected in America, Adams and Abigail finally return to Boston, where Adams is given a hero's welcome while reconnecting with his children.

In the Adams' new home, Peacefield, John deals with family concerns – including son Charles' debauched behavior at Harvard, John Quincy's courtship of a young woman, and the overtures being made by his aide, Col. William Smith, towards Adams' daughter, Nabby. Though he vows to remain "unemployed," Adams soon realizes that he and Abigail weren't meant "to sit in the shade of life." The election of the first U.S. President and Vice-President is at hand – and Adams will again be putting his private life on hold.