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In the 1760s the Stamp Act and the Townshend Acts, combined with other frustrations, were causing anger against England in the colonies, Philadelphia included. Both the Stamp and Townshend Acts led to boycotts of the importation of British goods. After the Tea Act in 1773, there were threats against anyone who would store tea and any ships which brought tea up the Delaware. In December, after the Boston Tea Party, a shipment of tea had arrived on the ship the Polly. The captain left after a committee told him to leave without dropping off his cargo.

A series of acts in 1774 further angered the colonies and there was a call for a general congress. The Massachusetts Assembly of June 17, 1774 suggested the general congress meeting be held in Philadelphia. The First Continental Congress was held in September in Carpenters' Hall. The American Revolutionary War began after the Battles of Lexington and Concord in April, 1775 and the Second Continental Congress met the next month at the Pennsylvania State House where they would sign the Declaration of Independence more than a year later. Besides being the location of the Continental Congress, Philadelphia was important to the war effort, as Robert Morris described "You will consider Philadelphia, from its centrical situation, the extent of its commerce, the number of its artificers, manufactures and other circumstances, to be to the United States what the heart is to the human body in circulating the blood."

Philadelphia was vulnerable to attack by the British. There were efforts to help protect the city from invasion from Delaware Bay and to recruit more soldiers, but there was no serious defense for the city. In March 1776 two British frigates began a blockade of the mouth of Delaware Bay and the British were moving south through New Jersey. In December the fear that the city was about to be invaded led to half of Philadelphia's population fleeing the city, including the Continental Congress which had fled to Baltimore. General George Washington pushed back the British advance at the Battles of Princeton and Trenton and the refugees and Congress returned. In September 1777 the British invaded Philadelphia from the south. General George Washington intercepted them at the Battle of Brandywine but was driven back. Thousands fled north into Pennsylvania and east into New Jersey; Congress fled to Lancaster then to York. British troops marched into the half-empty Philadelphia on September 23 to cheering Loyalists crowds.

The occupation lasted ten months; with the French now helping the Americans, the last British troops pulled out of Philadelphia on June 18, 1778 to help defend New York City. The American troops arrived the same day and began reoccupying the city under supervision of Major General Benedict Arnold, who had been appointed the city's military commander. The city government returned a week later and the Continental Congress returned in early July. While no longer under serious threat by the British, Philadelphia was experiencing serious inflation issues, with the poor suffering the worst. This led to unrest in 1779, with people blaming the upper class and Loyalists. One riot in January which had sailors striking for higher wages ended up dismantling ships. The Fort Wilson Riot on October 4 had a group of men target James Wilson, a signer of the Declaration of Independence but accused of being a Loyalist sympathizer. Soldiers broke up the riot, but five people had died and seventeen were injured.