[5] The pass separates four regions, the Tanana Valley to the north, the Delta Mountains to the east, Copper River Basin to the south, and the Hayes Range to the west.

[2][3] It is approximately bounded by Phelan Creek sourced by the Gulkana Glacier at the south, to Donnelly Dome to the north.

The Denali Fault approximately bisects the pass, near Miller Creek, just south of Canwell Glacier.

[13][14] Isabel Pass was formed predominately by the Delta River, with intermittent contribution from Phelan Creek, in the early Oligocene as the Alaska Range was beginning to be uplifted.

[16] Additionally, Ahtna and Middle Tanana place names of the surrounding area describe land features formed by ice that no longer exists, which suggests that they have been living in the area since at least the last ice age: In ancient times, outlier mountains proximate to major passes through the Alaska Range would have been known by every Dene foot traveler as important landmarks.

If a Dene traveler were walking north or south through Isabel Pass in the Alaska Range, the isolated mountain Donnelly Dome, Łuu Tahwdzeey’ (Middle Tanana) and Łuu Tahwdzaeye’ (Ahtna) for ‘heart among glaciers’, would be a foremark or backmark walking north or south between the Tanana and Copper River drainages.

and Isabelle Barnette crossed the pass on their way to Valdez and onto Puget Sound to purchase supplies for the newly formed city.

[22] In general, the roadhouses along the pass proved to be invaluable to travelers, providing shelter from strong winter storms.

[21]: 176–201 In 1903, Lieutenant William Mitchell, Judge James Wickersham, and several Fairbanks residents testified to a senatorial party visiting Alaska, pressuring them for transportation infrastructure.

By early 1905, Major Wilds Richardson was appointed by President Teddy Roosevelt to supervise construction of an all-season wagon road from Valdez to Fairbanks, which was completed in 1910 .

[8] In mid July of 2022, heavy rain in throughout the pass caused flash flooding and mudslides, leading the closure of the Richardson Highway.

Internet and cell phone interruptions were also reported due to a damaged fiber optic cable.

[14][13] On July 21, Governor Mike Dunleavy declared a state disaster, with costs associated with repairing the damages to be over $10 million.