Father Junípero Serra was born Miguel Joseph Serra in Spain in 1713. Educated as a friar in the Order of St. Francis, he immigrated to New Spain in 1749, where he worked as both a missionary and a university administrator. In 1769, Serra led a group of Franciscan monks into Alta California, and there oversaw the founding and maintenance of a chain of missions along the Californian coast. Mission San Gabriel was the fourth mission to be built in this chain. While Serra selected the site for the mission (a site that was eventually changed) he did not personally visit the mission station until September 1772, a year after its founding.

Serra oversaw a mission system that rapidly transformed the environment and living situation of California's indigenous communities. The friars, and the soldiers sent to accompany them, brought European domestic animals—cows, pigs, and sheep—into the region where they quickly reproduced past the point of containment. Non-native species of grasses and weeds were transported via supplies from New Spain and overran the local flora upon which Native communities depended for food. Thousands of indigenous people were pushed by these events to move to the missions in order to secure the means of their subsistence.

The friars forced Native people to work for the missions, often growing the crops upon which the mission community depended. The Franciscans strove to convert Native people to Catholicism, requiring that individuals attend mass, memorize catechisms, confess their sins, and accept harsh physical punishment for behaviors the friars considered sinful. Kinship structures were deeply disrupted by the friars' attempts to remake Native families according to a Christian, Spanish model. This situation was further compounded by mortality rates at the missions, which vastly outpaced those in other areas of the Spanish empire or Europe itself. Infants and children were especially vulnerable. The rampant spread of diseases such as syphilis and gonorrhea among the Native population made it hard for communities to replace the members they lost.

Native people were not passive in the face of such change. Many individuals sought to preserve their traditional spiritual belief systems—some of which, like that of the Luiseño, mapped easily onto the central ideas of Catholicism, and some of which did not—as well as offering political resistance to the authorities of New Spain. The environmental and epidemiological changes brought about by the missions, however, made it difficult for families or communities to survive without some connection to the missions, be it wholesale removal or trade.

Serra died in California in 1784. In 1987 he was beatified by Pope John Paul II, a prerequisite for the attainment of sainthood. Controversy persists as to whether Serra should be sainted, given his administration of a mission system that was so destructive to the lives of California's Native people.

The Treaty of Paris, adopted at the end of the French and Indian War (1754-1763), transferred control of Canada from France to Britain. After the United States later declared independence from Britain, France began offering secret support to the Patriots in the forms of arms, ammunition, economic aid, and technical assistance. Although the French government did not support Native Americans against the United States, some of the French Canadians (Canadiens) who had remained in Canada after the British takeover fought alongside Native American allies against the Patriots.

After acquiring Canada, the British had treated the Canadiens mildly. They allowed the former French citizens to continue practicing their Roman Catholic religion, and although the British required all residents of Canada to use the common law for public and criminal issues, they retained French civil law for private legal matters.

These measures helped the British to win the loyalty of many French Canadians. At the beginning of the Revolution, an American raid on Fort St. Jean, not far from Montreal, alarmed British officials and turned some Montreal residents against the Patriots. America’s wartime exclusion from the British fur trade benefited Montreal merchants, and despite lingering resentment over Britain’s possession of their colony, they decided that their own business interests lay with the preservation of British ties. Other French Canadians followed their religious and political leaders to the British side. Americans, after all, were the same people the Canadiens had just fought in the French and Indian War, when British New Englanders committed such atrocities as seizing farms, livestock, and produce, and stabling horses in their Catholic churches. Canadiens believed that they were better off with the British conquerors than with the American Revolutionaries.

In the territory bordering Canada and the new United States, the Six Nations of the Iroquois were also forced to make decisions with regard to alliances. Although many preferred to remain neutral, Tuscaroras and Oneidas generally chose to ally with the Americans. The rest of the Six Nations, led by the Mohawks, supported the British. Molly Brant, a respected Mohawk and mistress to British Indian Superintendent Sir William Johnson, and her brother Mohawk war chief Joseph Brant (Thayendanegea), convinced the Mohawk to side with the British. In several battles, Iroquois warriors, British regulars, and Canadien militia fought together to retain control over territory far down into Ohio Country and into the area around present-day Detroit.

Although some Canadiens fought with the British, others fought with the Patriots. For example, the 1st Canadian Regiment included Canadiens sympathetic to the American cause. They saw action in the Battles of Quebec (1775), Trois-Rivieres (1776), and Saratoga (1777), among others.