In the late 1890's, Wrangell once again became the base of operations for prospectors travelling up the Stikine River to strike it rich in the famous 1898 Klondike gold rush. There were three different routes to the Klondike. The first was the Stikine River route which already had been the site of two rushes. Wrangell was advertised in newspapers as the easiest and the all Canadian route to the Klondike, prompting thousands of miners to go to Wrangell in 1897. Another later route was from Skagway and over the White Pass, and the last was from Dyea up the Taiya River and over the Chilkoot Pass. From 1897 until 1900, Wrangell was a vital supply point for miners heading to the Klondike.

Wrangell served as the center for all the gold rushes, until Skagway came into existence to support the last gold rush to the Klondike area. The only other large town in Southeast Alaska at that time was Sitka. Neither Juneau nor Ketchikan or Petersburg was in existence. Wrangell was the economic center for Alaska, providing lodging, supplies, equipment and entertainment to thousands of miners. At one point over 10,000 persons were in Wrangell at one time, waiting for supplies and transportation up the Stikine. Cottonwood Island, near the mouth of the Stikine River, became a makeshift "tent city" for prospectors waiting for the spring thaw so they could travel up the river to the mining areas.

Buck Choquette, who discovered gold in the first rush, participated in all of the rushes that followed. Famed lawman Wyatt Earp travelled through Wrangell during the Klondike rush, and filled in as Deputy Marshal of Wrangell for ten days. Unfortunately records don't show anything particularly noteworthy that happened while he was here, perhaps his reputation as a lawman deterred any criminal acts. Instead he and his wife Josie turned back to San Francisco after learning that she was pregnant.

A number of buildings from the Klondike gold rush time period still exist in Wrangell. Norris' Gift Shop, in the heart of downtown, got its start as the Fort Wrangel Brewery Beer Hall. In one ad from the Stikeen River Journal in 1898, Bruno Grief, Proprietor says "It is a pleasure to take up one of those big, foaming mugs and look for the bottom...I wish my throat was a yard long every time I tackle one of Bruno's best" (after Cohen 1986). Keg beer sold for 40 cents a gallon, bottled beer was $1.50 per dozen. The brewery shared the street with The Totem Pole Drug Store, owned and operated by Dr. R. B. Davy. The drug store offered "photographic views and Indian Curios" (Fort Wrangell News, Oct. 26, 1898) to the tourists. Another historic building, now J.R.'s Fish Company, was built in 1898 by R.C. Diehl, a name mysteriously misspelled on the building as R.C. Biehl shortly after construction and never corrected.

Between 1898 and 1900, there were discussions to build a railway to take miners to the Klondike from Wrangell. A road up the Stikine River from Wrangell would meet up with the proposed railway. Instead, Skagway's route turned out to be shorter, more expedient to build and with more political clout. Even before the gold rush ended in the Klondike, it ended for Wrangell as the miners headed to the new town of Skagway. The community of Wrangell took it in stride and turned its attention to fishing and logging. Until the late 1990's, there was still an operating mine on the Iskut River in British Columbia, a tributary of the Stikine River, and Wrangell served as its supply and transshipment point. Wrangell continues to serve as the gateway to the magnificent Stikine River.

Note: Before 1902, when the Post Office officially shortened and respelled "Wrangell", it was called Fort Wrangel, with only one "l". The fort was named by the American Army after Baron Von Wrangel' (Russian spelling), who was the governor/general of Russian America from 1830 to 1835.