Upon Keith's arrival in San Francisco the job he had hoped for did not materialize, so he set up his own engraving business.

While there, Keith studied under Albert Flamm, but also wrote enthusiastically in letters about the free, "suggestive" brushwork of Andreas Achenbach.

[2] Keith then returned to California, and traveled to Yosemite Valley with a letter of introduction to John Muir.

James Mitchell Clarke described their friendship as one "in which deep affection and admiration were expressed through a kind of verbal boxing, counter-jibe answering jibe, counter-insult responding to insult.

"[4] During the 1870s Keith painted a number of six- by ten-foot panoramas, including Kings River Canyon (Oakland Museum, originally owned by Governor Leland Stanford) and "California Alps" (Mission Inn, Riverside).

He turned for comfort to a friend, the Swedenborgian minister Joseph Worcester, who ultimately had a strong influence on Keith's approach to landscape painting.

In 1883 Keith married Mary McHenry, who was the first female graduate of Hastings Law School and a leading suffragist.

A few months later they traveled to the East Coast and then to Munich, where Keith was determined to learn figure and portrait painting.

He primarily worked on his own, occasionally receiving criticism from artists including Carl von Marr and J. Frank Currier.

Through Joseph Worcester, Keith met the architect Daniel Burnham in Chicago while en route to Europe.

Burnham became an important patron and agent, showing and selling Keith paintings to collectors in the Chicago area.

Muir encouraged Keith to depict mountain scenery realistically, but as Keith's artistic sense had matured, he felt free to depart from geologic reality, placing an imagined glacier or a river in a scene to enhance the beauty of the painting.

William would goad Muir by responding, 'Look here now, John, if you'll go out early tomorrow morning and look toward the East you'll see nature imitating my sunrise.".

In the 1890s and early 1900s Keith painted landscapes of Carmel Bay and Cypress Point from his trips to the Monterey Peninsula.

According to James,[T]hese two citizens, lovers of his work, early in the day diverted their attention from all other interests, their own private ones included, and made it their duty to visit every place which they knew to contain a Keith painting.

[12]These benefactors presented the recovered paintings to Keith, who was then working from his primary studio at his Berkeley home.

"[12] This experience led to Keith's promise, despite his declining health, to replace for his buyers all paintings lost during the fires.

Linnie Marsh Wolfe wrote that Keith "left behind all his synthetics of the last twenty-five years and humbly, reverently portrayed what he saw, as objectively as in the seventies when Muir first infused into him his own spirit and vision.

The best way to do that is to be near her, and I have vague ideas about living in such close communion with her that she may adopt me and show me things hidden to every eye but that which loves her sincerely.