Anne Keilway was sole heiress to her father, and on his death in 1581 brought Harington possession of Combe Abbey. Before he succeeded his father in 1592, Harington probably spent the greater part of his time in Warwickshire, and in September 1586 he was chosen to escort Mary Queen of Scots through the county on her way from Staffordshire to Fotheringay.
On the accession of James I, Harington travelled to Yorkshire with his younger brother James to meet the King, later entertaining him to dinner at Burley, his second Rutland residence. In June 1603 the young Princess Elizabeth stayed at Combe Abbey, and shortly afterwards, at the coronation, Harington was raised to the peerage as Baron Harington.
The following October he was appointed guardian to the Princess. At the time of the Gunpowder Plot, when news reached him at Combe Abbey that the conspirators planned to abduct his charge and enthrone her after the explosion, he removed her to Coventry two hours before their arrival at his house.
In February 1613 Harington preceded her in her wedding procession to Whitehall, receiving from the bridegroom plate worth £2,000. In April 1613, with the honorary title of ambassador, though at his own expense, he accompanied the Elector and his bride to Germany, dying at Worms on the way home.