On 12 June 1881, Daniel Stott died of strychnine poisoning at his home in Boone County, Illinois, after Cream supplied him with an alleged remedy for epilepsy. The death was attributed to natural causes, but Cream wrote to the coroner blaming the pharmacist for the death after again attempting blackmail. This time, Cream was arrested, along with Mrs Julia A. (Abbey) Stott, who had become Cream's mistress and procured poison from Cream to do away with her husband. She turned state's evidence to avoid jail, laying the blame on Cream, which left him to face a murder conviction on his own. He was sentenced to life imprisonment in Joliet Prison.
One night unknown persons erected a tombstone at Mr Stott's grave which read, "Daniel Stott Died June 12, 1881 Aged 61 Years, poisoned by his wife and Dr Cream."
Cream was released in July 1891. Governor Joseph W. Fifer had commuted his sentence after Cream's brother pleaded for leniency and allegedly bribed the authorities.
Using money inherited from his father, who had died in 1887, Cream sailed for England, arriving in Liverpool on 1 October 1891.