The Oregon boundary dispute (often called the Oregon question) arose as a result of competing British and American claims to the Oregon Country, a region of northwestern North America known also from the British perspective as the Columbia District, a fur-trading division of the Hudson's Bay Company. The region at question lay west of the Continental Divide and between the 42nd Parallel of latitude on the south (the northward limit of New Spain) and the 54 degrees, 40 minutes line of latitude (the southward limit of Russian America).

Both the United Kingdom and the United States had territorial and commercial interests in the Oregon country as well as residual claims from treaties with Russia and Spain, who had abandoned their own claims to the region. In 1818 the United Kingdom and the United States agreed to share sovereignty in the region under terms of "joint occupancy", demurring on any resolution of the territorial and treaty issues until a later time. Negotiations over the next several decades failed to settle upon a compromise boundary and the Oregon Dispute became important in geopolitical diplomacy between the British Empire and the new American Republic.

American economic activity in the region until the 1840s was marginal, consisting of a Boston-owned fur trading post staffed by French Canadians at Fort Astoria, near the mouth of the Columbia River, as well as ongoing marine fur trade vessels. The British mandate was in the form of a licence held by the Hudson's Bay Company to trade with the populous aboriginal peoples of the region, and a network of trading posts and routes extended southward from New Caledonia, another HBC fur-trade district, into the Columbia basin. The HBC's headquarters for the entire region became established at Fort Vancouver (today's Vancouver, Washington), which became the centre of a thriving colony of mixed origin, including French Canadians, Hawaiians, Algonkians and Iroquois, as well as the offspring of company employees who had intermarried with various local native populations. Actual American settlers in the region were negligible until the advent of the Whitman Party, although American mythology holds that the Dispute over the region was due to increasing numbers of American settlers moving into the country, which was not actually the case until the 1840s.

In 1844 the U.S. Democratic Party, appealing to expansionist sentiment, asserted that the U.S. had a valid claim to the entire Oregon Country. Democratic presidential candidate James K. Polk won the 1844 election, but then sought a compromise boundary along the 49th parallel, the same boundary proposed by previous U.S. administrations. Negotiations between the U.S. and the British broke down, however, and tensions grew as American expansionists like U.S. Senator Edward Allen Hannegan of Indiana urged Polk to annex the entire Oregon Country up to latitude 54°40'N, as the Democrats had called for in the election. The turmoil gave rise to slogans like "Fifty-Four Forty or Fight!", often mistakenly associated with the 1844 election, and the catchphrase "Manifest Destiny".

The expansionist agenda of Polk and the Democratic Party created the possibility of two different, simultaneous wars, because relations between the United States and Mexico were deteriorating following the annexation of Texas. Just before the outbreak of the war with Mexico, Polk returned to his earlier position on the Oregon boundary and accepted a compromise along the 49th parallel. This agreement was made official in the 1846 Oregon Treaty, and the 49th parallel remains the boundary between the United States and Canada.

Meanwhile, many newspaper editors in the United States clamored for Polk to claim the entire region as the Democrats had proposed in the 1844 campaign. Headlines like "The Whole of Oregon or None" appeared in the press by November 1845. In a column in the New York Morning News on December 27, 1845, editor John L. O'Sullivan argued that the United States should claim all of Oregon "by the right of our manifest destiny to overspread and to possess the whole of the continent". Soon afterwards, the term "Manifest Destiny" became a standard phrase for expansionists, and a permanent part of the American lexicon. O'Sullivan's version of "Manifest Destiny" was not a call for war, but such calls were soon forthcoming.

In his annual address to Congress on December 2, 1845, Polk recommended giving the British the required one-year notice of the termination of the joint occupation agreement. In Congress, Democratic expansionists from the Midwest, led by Senators Lewis Cass of Michigan, Edward A. Hannegan of Indiana, and William Allen of Ohio, called for war with the United Kingdom rather than accepting anything short of all of Oregon up to 54°40'N. (54°40' was then the southern boundary of the Russian claim to Alaska.) The slogan "Fifty-Four Forty or Fight" appeared by January 1846, driven in part by the Democratic press. The phrase is frequently misidentified as a campaign slogan from the election of 1844, even in many textbooks. Bartlett's Familiar Quotations attributes the slogan to William Allen.

The calls to war were fueled by a number of factors, including traditional distrust of the British and a belief that the U.S. had the better claim and would make better use of the land. Moderates warned that the U.S. could not win a war against the world's greatest power, and that negotiation could still achieve U.S. territorial goals. Although the debate in the U.S. was not strictly divided along party or sectional lines, many who clamored for the 54°40' border were Northerners upset that Polk (a Southern slaveowner) had been uncompromising in his pursuit of Texas (a cause deemed favorable to Southern slaveowners), but willing to compromise on Oregon. As historian David M. Pletcher noted, "Fifty-Four Forty or Fight" seemed to be directed at the southern aristocracy in the U.S. as much as at the United Kingdom.