On the outbreak of the First English Civil War, Murray was sent by the king to Montrose to inform him and other friends in Scotland of the state of his affairs, and to procure their advice and help.

In 1645, Murray was with Queen Henrietta Maria of France in Paris, and was employed by her in her negotiations on the king's behalf with foreign powers, and with the Pope.

In October, Murray was sent back to London on a secret mission, which he undertook at some risk of "putting his neck to a new hazard," but on his return he informed the king "that the Scots commissioners hindered him to do anything therein for the little hope he could give them of his ratifying the covenant."

In 1648, Henrietta Maria sent him to Scotland to further 'the engagement', and to persuade his countrymen to receive the Prince of Wales, whom she wished to take part in the effort for the deliverance of the king.

He first tried to induce Argyll and the dominant party in the church to support the resolutions of the Scottish estates, but, failing in this, he took counsel with the Duke of Hamilton and his friends, and in May, he returned to the continent with letters from them formally inviting the prince to Scotland.

Among those who gathered round Charles II at the Hague immediately after his father's death, Lord Byron mentions "old William Murray, employed here by Argyll."

After the Scots commissioners returned unsatisfied in June 1649 from their visit to the Dutch Republic, Charles sent over William Murray with private letters to Argyll and Loudoun.

It is to this period apparently that John Livingston refers in his 'Autobiography' when he says that William Murray and Sir Robert Moray, who had long been very intimate with Argyll, 'put him in hopes that the king might marry his daughter.'

As the patent did not pass the great seal, he ranked as a commoner till 1651, when, according to Lament's 'Diary', several of the gentry were ennobled by Charles II, and among them 'William Murray of the bedchamber, who was made Lord Dysart.'