With a strongbox full of gold under the driver's seat, the stagecoach pulled by a six-horse team was an icon of Western commerce and development. However, in the 19th century, the navigable Columbia and Willamette Rivers and a low demand delayed the appearance of stagecoaches in Oregon.

"I have not received any letters from you for two months," a Gold Rush miner wrote his wife. "I hardly know what to think." Delivering the U. S. Mail overland, under contract with the federal government, drew Wells Fargo into overland stagecoaching (and later, the Pony Express). In 1852, Wells, Fargo & Co. opened for business in San Francisco, and Portland soon became the hub of Wells Fargo's banking and express business in the Pacific Northwest. William H. Barnhart, a friend of Henry Wells and William G. Fargo, opened the Portland Wells Fargo office (or "agency") in his general store on Front Street. Agencies were often in a town's general store or hotel—in one instance, the local saloon! Barnhart bought and sold gold dust, delivered letters, transferred funds, forwarded packages, and even gave advice on the Oregon potato market.

Wells Fargo expanded slowly in rural Oregon during the 1850s, keeping pace with the lumber trade and coastal steamer stops. In 1857, the first Oregon stagecoach line ran between Portland and Salem, and Wells Fargo & Co.'s Express was aboard. Overland stagecoaches began competing with oceangoing steamships in September 1858—the frequency was superior. By the 1860s, stagecoaches moved more mail than steamers—deliveries increased from two times a month by sea to 26 times a month by land.

In September 1860, the California Stage Co. linked Sacramento and Portland. At 710 miles, it was the second longest stageline in the nation. The company had 28 coaches, 30 stage wagons, 35 drivers, 14 district agents, 75 hostlers, and 500 horses. To the east, in 1864, Wells Fargo inaugurated expresses from The Dalles through Canyon City and from Umatilla by way of Baker City, both into Idaho. Wells Fargo's Express rode in other stagelines across Oregon. "Having opened offices at Forest Grove, Hillsboro, Lafayette, McMinnville, Butteville, and Dayton," Wells Fargo advertised in 1868, "we will dispatch an Express [from Portland] every Monday and Thursday morning ... "

"On the afternoon of the 8th of October, I left Portland for San Francisco by the overland route ... I took a seat in a coach of the California and Oregon Stage Company to commence my long ride ... Four gentlemen and two ladies with children occupied the inside while the driver had plenty of company on top ... Careful driving is required on these mountain roads, necessarily narrow in the most dangerous places, so that a few inches divergence from the single track would be a sure upset into the ragged abysses of darkness below. The night was radiant. I never saw more brilliant heavens, even in the tropics, than on the Oregon Mountains."

—Frances Fuller Victor, 1870

By 1880, Wells Fargo had 50 offices in Oregon, and within three years the company operated 75 express offices linked by stagecoach, steamer, and railroad. Stagecoaches kept rolling until the completion of the north-south railroad in December 1887. Even after the railroads came, the Wells Fargo stagecoach continued to roll in Portland's seventh annual Rose Festival in June 1913.