Talbot was the only son of Francis Talbot, 5th Earl of Shrewsbury. In 1560, he inherited the Earldom of Shrewsbury, the Barony of Furnivall and the position of Justice in Eyre, which had been his father's. One year later, he was created a Knight of the Garter, and in 1567, he married Bess of Hardwick in a double wedding with their two eldest children from previous marriages. However their marriage was marred by Lord Shrewsbury's selection as the keeper of Mary, Queen of Scots (who was effectively exiled by Queen Elizabeth I).
Meanwhile, in 1571, Lord Shrewsbury was appointed Lord High Steward (the premier Great Office of State) for the trial of Thomas Howard, 4th Duke of Norfolk (regarding the Ridolfi plot). Finally, in 1572, Lord Shrewsbury was appointed Earl Marshal, a position that he held (along with the aforementioned position of Justice in Eyre) until his death in 1590. Upon his death, his eldest son, Gilbert Talbot (from the marriage with Gertrude Manners), inherited the earldom. He was buried in the Shrewsbury chapel at Sheffield Parish Church (now Sheffield Cathedral), where a large monument to him can still be seen.