In 1844, William Still moved to Philadelphia, Pennsylvania, where he began working as a clerk for the Pennsylvania Anti-Slavery Society. When Philadelphia abolitionists organized a committee to aid runaway slaves reaching Philadelphia, Still became its chairman. By the 1850s, Still was a leader of Philadelphia's African-American community. In 1859 he attempted to desegregate the city's public transit system. He opened a stove store during the American Civil War, and later started a coal delivery business.

In 1847 he married Letitia George and had four children who survived infancy. Their eldest was Caroline Matilda Still (1848—1919), a pioneer female medical doctor. Caroline attended Oberlin College and the Women's Medical College of Philadelphia (much later the Medical College of Pennsylvania); she was married, first to Edward J. Wyley, and after his death, to the Reverend Matthew Anderson, longtime pastor of the Berean Presbyterian Church in North Philadelphia. She had an extensive private medical practice in Philadelphia and was also a community activist, teacher and leader. William Wilberforce Still (1854—1914) graduated from Lincoln University and subsequently practiced law in Philadelphia; Robert George Still (1861—1900), was a journalist who owned a print shop on Pine at 11th Street in central Philadelphia and Frances Ellen Still (1857—1930) became a kindergarten teacher (she was named after poet Frances Ellen Watkins Harper, who lived with the Stills before her marriage). On the 1900 U.S. Census William Still said he had two children and both were still living.

Underground Railroad

Often called "The Father of the Underground Railroad," Still helped as many as 60 slaves a month escape to freedom, interviewing each person and keeping careful records, including a brief biography and the destination of each person, along with any alias that they adopted, though he kept his records carefully hidden. He is one of the many who helped slaves escape from the United States. During one interview of an escapee, he discovered that the man, Peter Still, was his own brother. They had been separated since childhood, and his brother knew little about the rest of his family. Still later published The Underground Rail Road Records, which chronicles the stories and methods of 649 slaves who escaped to freedom via the Underground Railroad. Peter Still later collaborated on a book detailing his experiences. He helped people find their way to freedom.

The three prominent Still brothers—William, James, and Peter—settled in Lawnside, New Jersey. To this day, their descendants have an annual family reunion every August. Notable members of the Still family include the composer William Grant Still.