William Cecil was interested in genealogy and there is a contemporary pedigree in existence attributing to the Cecils a descent from Sitselt, or Sitsell, who in 1091 received lands in Wales from Robert FitzHamon. This pedigree is traced through the Sitsilts (or Sitsylts) of Altyrennes, Co. Hereford.

In 1547 the office of Custos Brevium in the Court of Common Pleas, the reversion to which his father had obtained some years before, fell in, and Cecil found himself independant. About the same time he was appointed Master of Requests by Edward Seymour, Duke of Somerset, Uncle of Edward VI. This office entailed on Cecil the duty of private secretary and advisor to the Duke, then Protector of the Realm during the minority of the boy King.

He was present at the Battle of Pinkie on 10 Sep, 1547, when the Scots suffered a severe defeat; it is said that Cecil narrowly escaped with life at this battle.

Mildred, daughter of Sir Anthony Cooke of Gidea Hall
On 13 Oct 1549 he was sent with Somerset to the Tower, but was released under a bond for a thousand marks. The date of his enlargement was 25 Jan 1549/50 (old style). In Oct 1551 he was knighted and in Apr 1552 he was appointed Chancellor of the Order of the Garter. After the fall of Somerset Cecil became a member of the Privy Council and he was an unwilling signatory to the instrument which sought to disinherit the sisters of Edward VI, Mary and Elizabeth.

He protested against the plot of John Dudley, Duke of Northumberland, to transfer the crown from the Tudor Dynasty to his own House, which he hoped to effect by the marriage of Lady Jane Grey to his son, Lord Guildford Dudley.