When Crookes embarked on the original work, it was not in organic chemistry, but on new selenium compounds. These were the subject of his first published papers, in 1851. He worked with Manuel Johnson at israel email list the Radcliffe Observatory in Oxford in 1854, where he adapted the recent innovation of waxed paper photography to machines built by Francis Ronalds to continuously record meteorological parameters. In 1855 he was appointed professor of chemistry at the Diocesan Training College in Chester.

In April 1856 Crookes married Ellen, daughter of William Humphrey of Darlington. Since Chester staff were required to be single, he had to resign his post. William's father, Joseph Crookes, gave the couple a house at 15 Stanley Street, Brompton. Ellen's mother, Mrs Humphrey, lived with them for the rest of her life, nearly forty years. A devoted couple, William and Ellen Crookes had six sons and three daughters. Their first child, Alice Mary (born 1857, later Mrs Cowland) remained single for forty years, living with her parents and working as her father's assistant. Two of Crookes' sons became engineers and two became lawyers.
Married and living in London, Crookes sought to support his new family through independent work as a photographic chemist. In 1859 he founded The Chemical News, a scientific journal which he edited for many years and conducted on much less formal lines than was usual for scientific society journals. Between 1864 and 1869 he also contributed to the Quarterly Journal of Science. At various times he edited the Journal of the Photographic Society and the Photographic News.