An important event that the people of Nueva Espana largely ignored was the declaration of independence by the 13 British colonies of the East Coast in 1776. The USA was born, with its capital in Philadelphia, much smaller than Nueva Espana at the time. The two bordered because Nueva Espana had expanded westward in 1763 to the Mississippi river, which was the eastern border of Virginia, Georgia and North Carolina, three of the British colonies now part of the USA.

In 1803 the USA (Thomas Jefferson) purchased Louisiana from France (Napoleon), which had purchased it back from Spain in 1800. That "Louisiana" included 13 of today's states: Montana, North and South Dakota, Minnesota, Iowa, Wyoming, Nebraska, western Colorado, Kansas, Missouri, Arkansas, Oklahoma and Louisiana. The border between the USA and Nueva Espana was now at the Rocky Mountains.

Meanwhile, the Russian colonization of Alaska began in earnest. In 1784 the merchant Grigory Shelikhov established Russia’s first permanent settlement in Alaska, and Russian "promyshlenniki" began trickling down the coast to north California looking for the pelts of sea otters and fur seals, and frequently indenturing native Aleut hunters to hunt furs for them. In 1799 the czar gave his blessing to the Russian-American Company, which was also Russia's first joint-stock company. Russian merchants spread as far south in California as Fort Ross in 1812, about 100 kilometers north of the San Francisco Bay. Nikolai Rumyantsev as Minister of Commerce funded Russia's first circumnavigation of the Earth in 1803–1806 (led by the Estonian officer Adam-Johann von Krusenstern and the Ukrainian officer Yuri Lisyansky) and as Minister of Foreign Affairs funded the "Rurik" circumnavigation (led by the Estonian officer Otto von Kotzebue) in 1815-18. The latter failed in its main mission (to discover the "Northwest Passage" between the Atlantic and Pacific oceans via the Arctic waters) but provided precious information about Alaska's and California's geography, flora, fauna and people. (Russia maintained possession of Alaska until 1867 when it sold it to the USA).

Another explorer looking for the Northwest Passage was a Briton, Alexander Mackenzie, who in 1792-93 managed to cross British Canada from the Atlantic to the Pacific, possibly the first person ever to do so and certainly the first European ever.

The naval British expedition of the Pacific Coast, led in 1791-95 by George Vancouver (who had served under James Cook), which reached America via Africa, Australia and Hawaii, resulted in the first detailed maps of the coast from today's Marin County to today's British Columbia, published in 1798 after his death as "Voyage of Discovery to the North Pacific Ocean and Round the World".

Both Spain and Russia had long claimed the Pacific coast north of Alta California, but Spain was too south and Russia too north, whereas Britain had Canada. The new country of the USA had its own interest: trading with China. The war of independence ended in 1783 with the USA doubling in size because it acquired the British region north of the Ohio River and east of the Mississippi and south of the Great Lakes (renamed Northwest Territory in 1789). Chinese tea was one of the commodities in high demand in Europe (after all, the whole war against Britain had started with the "Boston Tea Party"). Britain was buying tea from China by selling Indian-grown opium to China. The USA, however, had to pay for tea with silver coins. In February 1784 the ship Empress of China, commanded by captain John Green, left New York with a cargo of mainly ginseng, pelts, bullion and silver. It sailed east across the Atlantic to the Cape Verde islands, then rounded the Cape of Good Hope and crossed the Indian Ocean to reach Canton/ Guangzhou in China in August. Since 1757, Canton was the only city in China that the emperor allowed to trade with foreigners. In December the ship sailed back, reaching New York in May 1785, carrying lots of tea and "exotic" Chinese goods: that expedition had discovered that the Chinese also wanted ginseng, bullion and fur, and the investors soon discovered that their fellow Americans wanted Chinese lacquerware and porcelain. The Empress of China had inaugurated direct US-Chinese trade and had breached the British monopoly on the tea trade. It also transported Samuel Shaw, the first official representative of the US government, who in 1792 was formally appointed ambassador to China.

In October 1787 John Kendrick sailed from Boston on the ship Columbia Rediviva, the first US ship to round the Cape Horn, and in August 1788 reached the region that the Anglosaxons called Oregon (an English misspelling of the Algonquian name of a river flowing east to west). Robert Gray completed the voyage to Canton in 1789 (from July to December) with a cargo of Oregon furs, traded the furs for tea, and returned to Boston in August 1790 via the Cape of Good Hope, thus becoming the first US captain to achieve the circumnavigation of the Earth. Gray sailed again for another circumnavigation a few weeks later (October 1790), arriving in Oregon in June 1791, exploring the still unexplored Columbia River in May 1792 (hence the name of the river), sailing to Canton and then around the Cape of Good Hope across the Atlantic back to Boston in July 1793.

In 1800 the New York fur trader John Jacob Astor (born in Germany and raised in Britain) imitated the Empress of China with his own Canton-bound ship full of fur and opium. Astor made a fortune trading Canadian fur in New York, London and Canton and became the first multi-millionaire of the USA. Of course, it would have been easier and faster to ship fur to China from the Pacific coast.

John Meares, an illegal English fur trader based in India, led an expedition in January 1788 from Portuguese Macau (he couldn't sail as a British citizen because the East India Company held a monopoly on British trade in the Pacific) to Nootka Sound (near today's Vancouver), arriving in May 1788. His ships carried 50 Chinese sailors and laborers who built the first ship ever built by Europeans or Asians in the Pacific Northwest, using materials that they carried with them from China. It sailed in September 1788 towards the Sandwich Islands. Those 50 Chinese were probably the first Chinese to visit the Pacific Northwest.

The ability of the USA to sail to California was indirectly helped by the Barbary Wars. Four Muslim states of North Africa, known as the "Barbary States" (Morocco, which was already independent, and the Ottoman provinces of Algiers, Tunis and Tripoli) had been practicing piracy for centuries. They not only stole cargoes but even sold sailors as slaves. They mostly demanded that European nations pay ransom, or, still better, annual tribute. In 1801 one of the Barbary States (that was already at war with Sweden) even declared war on the USA because the USA refused to pay the requested ransom. US president Thomas Jefferson launched an attack using Sicily (then part of the Spanish kingdom of Napoli) as a military base. The USA took four years but in 1805 the pasha capitulated. It was the first war fought by the USA outside America. It was also the first time that US soldiers fought together as USA rather than separately as New Yorkers, Texans, Virginians, etc. The victory excited the US public.

At the same time, Thomas Jefferson dispatched Meriwether Lewis and William Clark to scout the route from Illinois to the Pacific Ocean in 1804-05, the first official exploration by the USA of the Oregon Country (today's states of Washington, Oregon and Idaho). The Anglosaxons ignored the southern route through California that still belonged to Spain.

Tired of the long route to China via Africa, Astor had the idea of establishing a fort/port in Oregon to trade fur directly across the Pacific to China. In 1810 he organized a double overland expedition, one by sea via Cape Horn which reached Oregon in March 1811 and founded Fort Astoria at the mouth of the Columbia River (the first US settlement on the Pacific coast) and one overland, which arrived at Astoria in January 1812. Alas, his venture was doomed by the war of 1812 between the USA and Britain. More than sixty men had died in the exploration. The war was caused by British arrogance: between 1807 and 1812 Britain had seized some 400 merchant ships of the USA, and between 1803 and 1812 more than 6,000 US sailors had been kidnapped and forced to work on British ships (Britain didn't have enough sailors). In 1812, while Britain was consumed by the Napoleonic wars, the USA decided to take action. Since the USA only had 16 warships, it opted for waging war overland, invading British Canada. The war raged for two years from the Canadian border to New Orleans, and the British even raided Washington, setting the Capitol and the White House on fire, but the war ended with no winner. It did end with some losers: the "Indian" tribes who sided with the British, which were annihilated and lost their lands. Future president William Henry Harrison, governor of the Indiana Territory, defeated the confederation created by chief Tecumseh in the north (the war had started in 1810 but ended in 1813) future president Andrew Jackson defeated the Red Sticks in Alabama in 1813-14 (he then defeated the British at the Battle of New Orleans in January 1815). Those Indian wars helped open the route to the Far West. In 1818 the USA and Britain, having finally made peace, reached an agreement to jointly settle the Oregon Country all the way to the 49th parallel north (which became the border with British Canada). Oregon provided the USA with access to the Pacific Ocean.

In 1823 the Franciscan missionary Jose' Altimira established Mission San Francisco Solano de Sonoma north of San Francisco, the only new mission established after Mexico's independence, California's northernmost and its last one.

A crisis between the USA and Spain over Florida almost erupted into another war but this time the two countries reached an agreement in 1819: Florida became a state of the USA and a border was agreed upon between the USA and Spanish California. In particular, the 42nd parallel became the northern limit of Nueva Espana (i.e. the border between California and Oregon). Spain finally renounced any claims on Oregon Country, and Russia gave up its claims too.

Spain lost Nueva Espana two years later. In 1821 the creole Augustin de Iturbide and the mestizo Vicente Guerrero declared the independence of Nueva Espana, and declared a Mexican Empire (Mexico, California, Texas, Central America). Alta California was now part of the independent country of Mexico, and its capital was Monterrey.

In 1829-30 a Spanish merchant named Antonio Armijo led the first caravan from near Santa Fe in Nuevo Mexico to San Gabriel Mission in Alta California, opening what would be known as the "Old Spanish Trail" (about one thousand kilometers). The journey took about three months. Traders were selling blankets and clothes to Alta California, and were buying horses, mules and Paiute slaves.

The interest of the USA in exploring the Pacific Ocean was still minimal, but increasing. In 1821 US president James Monroe, the man who had negotiated the Louisiana Purchase when Jefferson was president, established the Pacific Squadron, tasked with protecting US commerce with Asia. The only lucrative trade with Asia was with China for tea. Ten years later, when Jackson was president, the Pacific Squadron carried out a military mission against pirates in Sumatra (one of the Indonesian islands) by sailing from New York via the Cape of Good Hope and the Indian Ocean to Sumatra (and then via the Pacific Ocean and Cape Horn back to New York six months later, another circumnavigation). In September 1826 the warship USS Vincennes sailed from New York for Cape Horn for the Pacific Ocean, which it patrolled for three years. It then reached China in 1830 and sailed for New York via the Indian Ocean and the Cape of Good Hope, becoming the first US warship to circumnavigate the Earth. At the time the Pacific Squadron was not interested in Alta California, which belonged to Mexico. It was interested only in protecting the trade between the East Coast of the USA and East Asia. Back then it took between four and seven months to to sail from the East Coast ports to Alta California, and there was little reason to do so.

If Spain, France, Russia, Britain and the USA were only hesitantly exploring California, there was one power that showed absolutely no interest in California despite being located across the ocean and being frequently visited by ships coming from California: China, ruled since 1644 by a Manchu dynasty called Qing. The Chinese emperor should have been at least curious to find out more about the continent that had provided new crops like potatoes, corn and peanuts which had indirectly enabled the rapid increase of China's population during the previous century. But the emperor, Yizhu Xianfeng (Emperor Wenzong), was dealing with multiple crises: the two Opium Wars against the British Empire (1839-60) and the "unequal treaties" (the Treaty of Nanjing in 1842, the Treaty of Tientsin in 1858) which humiliated China, and the Taiping Rebellion (1851-64) and the Nian Rebellion (1851-68) which killed millions of Chinese.