The pair had been separated for seven years during which time Sarah had raised their son, Henry George Yesler (1845?-1859) in Ohio, while Henry searched the West for opportunities to set up his sawmill. Expecting to return from the Northwest soon, Sarah left 12-year-old George with relatives in Ohio. The Yeslers' son became ill and died in June 1859.
Upon her arrival in Seattle, Sarah became cook for the sawmill employees, and actively involved herself in the Yesler business enterprises. She was in the forefront of the suffrage movement, active in the Seattle Library Association, a founding member of Seattle's first benevolent organization, and at the center of life in Seattle.
The Yeslers were spiritualists who refused to join any church. They hosted spiritualist-astrologer W. E. Cheney's sessions at their house. The spiritualists believed in free love and Sarah formed a passionate attachment to at least one other woman, while remaining a loyal wife to Henry.
In the 1880s, the Yeslers resisted the anti-Chinese agitation. Sarah Yesler's Chinese cook sought refuge in her house and she protected him and refused to turn him over to a mob of men.
In the 1880s, she helped to found the Ladies Relief Society, which in turn founded the Seattle Children's Home, an orphanage, in 1885.
She died after several weeks of severe gastric illness, on August 28, 1887. She was 65. Her biographers, Linda Peavy and Ursula Smith, write:
"As the news [of her death] swept across Seattle, flags in the city and its harbor were lowered to half-mast as citizens mourned the woman who had given so much to them. Stores and businesses closed their doors out of respect for 'the aged lady' and hundreds poured through the doors of the Yesler mansion and into its north parlor..." (p. 176).