These colourful adventures are traceable to a popular ballad entitled Sir William Stanley's Garland, which exaggerates his three years away from England to "twenty one years travels through most parts of the world". This was recorded in 1800 and its contents published in 1801. There is no extant documentary evidence for these supposed adventures, but the stories were regularly repeated in 19th-century biographies of the sixth Earl.
After the death of his father in 1593, his elder brother Ferdinando Stanley, 5th Earl of Derby, inherited the Earldom and its estates, but he died a few months later in April 1594, leaving three daughters but no sons. Ferdinando's daughters claimed their father's estates, while William inherited the titles of an Earl of Derby and Baron Strange. A further complexity was that Ferdinando's eldest daughter Anne Stanley, Countess of Castlehaven, became officially the heir presumptive to Elizabeth's throne in 1596 on the death of her grandmother. A complex legal dispute followed, which dragged on for many years. This led to a judgement that the Isle of Man, a possession of the 5th Earl, was forfeit to the Queen. However, the Queen ceded her right to it in recognition of the Stanley family's services. Stanley was granted Lathom and Knowsley, with other lands and estates in Lancashire, Cumberland, Yorkshire, Cheshire,Wales, and elsewhere, while Ferdinando's daughters received estates linked to baronies and the Isle of Man, but they sold it to their uncle, the 6th Earl, and his title to it was later confirmed by James I. While retaining the title ofLord of Mann, Derby passed the administration of the Isle of Man to his niece, Anne Stanley. In 1612 he transferred the title to his wife, Elizabeth. Derby's assumption of the barony of Strange was not contested in his lifetime, but after his death it was determined to have been incorrect, and a new creation of the barony was given to his son.
The Stanley family, as the lawful heirs to the throne of England through Henry VIII's sister Mary Tudor, were suspected of Roman Catholic sympathies. There were many rumours surrounding the untimely death of Ferdinando Derby, who had been approached to lead an attempt to overthrow Queen Elizabeth, but had remained loyal to her. Due to the sudden and violent nature of his final illness, poisoning was widely suspected. Possibly because of the potential for military rebellion in alliance with Irish Roman Catholics, the 6th Earl was expressly forbidden by the Queen to take part in the Earl of Essex's campaign in Ireland. He therefore limited his involvement with national politics, devoting himself primarily to the management of his estates and his dominant position in local administration in Lancashire and Cheshire. In 1603 he became a member of the Privy Council of England
Queen Elizabeth eventually granted Derby the Order of the Garter, while James VI and I appointed him Lord Chamberlain of Chester. A few years after the death of his wife, when Derby was "old and infirm, and desirous of withdrawing himself from the hurry and fatigue of life" he assigned his estates to his son James, retaining an annuity of £1,000. He bought a house by the River Dee just outside Chester, where he lived in retirement until his death on 29 September 1642.