The 32 delegates from the Province of Canada, Nova Scotia, New Brunswick and Prince Edward Island had agreed at the close of the Charlottetown Conference to meet again at Quebec City (at the Old Parliament Building) October 1864. Newfoundland also sent two observers, but did not participate directly in the proceedings. British Columbia did not participate in the conference.
The conference began on October 10. It lasted for over two weeks. The major source of conflict at the conference was between those who favoured a "legislative union", i.e. a unitary state, such as John A. Macdonald, and those who favoured stronger provincial rights. The Conference tied in very closely with the discussions of the aforementioned Charlottetown Conference, as the topics being discussed in Quebec centred around whether the country should have a strong and single central government, or a more encompassing federal system. Representatives from the Maritimes and Canada East (now Quebec) tended to argue for provincial rights, fearing they would lose their cultural identity under a centralized unitary state. Macdonald thought the failure of a weak central power was evident in the American Civil War, which was still being fought in the United States as the delegates met in Charlottetown and Quebec. The delegates eventually compromised, dividing powers between a "general" parliament and "local" provincial legislatures. They also decided to have an elected lower house, the House of Commons, and an appointed upper house, the Senate, although there was considerable debate about how many senators each province would have. The Prince Edward Island delegation called for a scheme similar to the Triple-E Senate proposal of the 1990s. Eventually, a proposed structure for the government was written out in the form of the seventy-two resolutions at the end of the conference.
The conference ended on October 27, and the delegates returned to their provinces to submit the Seventy-Two Resolutions to the provincial legislatures, with 50 of the 72 being drawn up by John A. Macdonald. George-Étienne Cartier was largely responsible for convincing the French-Canadian members of the Legislature in Canada to accept the resolutions, even though he himself did not support such a strong central government. Albert James Smith led the opposition to Confederation in New Brunswick, while Joseph Howe led the opposition in Nova Scotia, but both of these provinces eventually agreed to join the union. Only Prince Edward Island rejected the resolutions. Canada, New Brunswick, and Nova Scotia then set about securing partial autonomy from the British government, which culminated in a third London Conference in 1866, and the British North America Act on July 1, 1867.