He took part in the abortive royalist uprising under Glencairn in 1654, and was one of those who urged Monck to declare a free parliament in England to facilitate the restoration. He sat in the Scottish parliament as member for Argyllshire from 1669 to 1674.
In October, 1672, as principal creditor to George Sinclair, 6th Earl of Caithness, he obtained the inheritance of his lands and properties. After the Earl's death without heirs, he became Earl of Caithness and Viscount of Breadalbane. In 1678 he married former Earl's widow, the Countess of Caithness, an economical step which saved him his obligation to pay her 12,000 marks a year. In 1680 he invaded Caithness with a band of 700 men and defeated and dispossessed the contingent of the Sinclairs. The natural heir, a younger son of the fifth earl however, was subsequently confirmed in his lands and titles by the Parliament of Scotland, so on 13 August 1681, Campbell obtained a new patent which made him Earl of Breadalbane and Holland, Viscount of Tay and Pentland, and Lord Glenorchy, Benederloch, Ormelie and Wick, in the Peerage of Scotland, with special power to nominate his successor from among the sons of his first wife. In 1685 he became a member of the Scottish privy council. Though nominally a Presbyterian he had assisted the intolerant and despotic government of the Duke of Lauderdale in 1678 with 1700 men.
He was reputed to own the best wig in Scotland and his influence, owing to his position and abilities, was greater than that of any man in Scotland other than his cousin, the Duke of Argyll, a relationship that irked him and lead to his continuous political manoeuvering to improve his lot. It was important that William III obtained his services in conciliating the Highlanders. Breadalbane at first carried on communications with Dundee and was implicated in the royalist intrigue called the Montgomery plot, but after the battle of Killiecrankie in July 1689 he made overtures to the government, subsequently took the oath of allegiance, and was entrusted with a large sum of money by the government to secure the submission of the clans. On 30 June 1691 he met the Jacobite chiefs; he persuaded them to refrain from acts of hostility till October, gaining their consent by threats and promises rather than by the distribution of the money, which, it was believed, he retained himself. When asked to give an account of the expenditure to parliament, he replied
Breadalbane had a reputation for double-dealing which led to a lasting belief that he had a direct hand in the Massacre of the Macdonalds of Glencoe in February 1692. In reality he was one of the few men to recognize the political damage the episode caused in the Highlands. However, the discovery of his negotiations with the Jacobite chiefs caused his imprisonment in Edinburgh Castle in September, but he was released when it was known that he had been acting with William's knowledge.
Breadalbane did not vote for the Union in 1707, but was chosen a representative peer in the parliament of Great Britain of 1713–1715. His cooperation with the English government in securing the temporary submission of the Highlands was inspired by no real loyalty or allegiance, and he encouraged the attempted French dissent of 1708, refusing, however, to commit himself to paper.
On the occasion of the Jacobite rising in 1715 he excused himself on 19 September from obeying the summons to appear at Edinburgh on the ground of his age and infirmity, but nevertheless the next day visited Jacobite camps at Logierait and Perth, his real business being, according to the Master of Sinclair:
He had taken money to provide 1200 men to the uprising, and only sent 300. His 300 men were withdrawn after the battle of Sheriffmuir, and his death, on 19 March 1717, removed the need for an inquiry into his conduct.
He married Mary, daughter of Henry Rich, 1st Earl of Holland, with whom he had two sons, Duncan, styled Lord Ormelie, who was passed over in the succession, and John Campbell, 2nd Earl of Breadalbane and Holland; he also had a son by Mary, the widow of the Earl of Caithness, by whom he had one son, Colin, the presumed ancestor of Sir Lachlan Campbell, one of the present contestants for the title of Earl of Breadalbane and Holland.