The Maclachlans were loyal Jacobites. They were said to have been present at the Battle of Killiecrankie in 1689. In the Jacobite Rising of 1715 Lachlan Maclachlan of that Ilk "signed the Address of Welcome to the Old Chevalier, the rightful King James VIII Stuart, on his landing in Scotland". Archibald Brown, in The History of Cowal, wrote, "The chief of MacLachlan appeared with the Earl of Mar at Sheriffmoor as Colonel in the Pretender's army, and for this act it is said Campbell of Ardkinglas followed MacLachlan like a sleuthhound for five years and shot him dead in 1720".

Lachlan, the seventeenth chief of Clan Maclachlan played a part in the Jacobite Rising of 1745, and lost his life leading the clan at the Battle of Culloden. Lord President Duncan Forbes estimated that the Maclachlan force of that time was about 200 men. In 1748, Rev. John MacLachlan of Kilchoan, in a letter to Rev. Robert Forbes, Bishop of Ross and Caithness, wrote,

I hope you'll take notice of Collonel MacLachlan of that Ilk, whom the newspapers and magazines neglected. 'Tis true he got but few of his clan rais'd, because most of them are situated amidst the Campbells. However he attended the Prince at Gladsmuir, and march'd with him to Carlyle, from whence he was detach'd by the Prince with an ample commission and 16 horses to lead on to England the 3,000 men that lay then at Perth... ...The Collonel join'd us again at Stirlin, and when we retir'd to Inverness the Prince made him Commissary of the army. At the battle of Culloden he had a regiment of 300 men, whereof 115 were his own people and 182 were Mackleans, who chose to be under his command, seeing their chief was not there. The said Collonel being the last that received orders from the Prince on the field of battle, he was shot by a canon ball as he was advancing on horseback to lead on his regiment, which was drawn up between the Macintoshes and the Stewarts of Appin.”

Following the Jacobite defeat a Government ship sailed up Loch Fyne and shelled Castle Lachlan, forcing the chief's family to abandon their residence, and in Edinburgh the Maclachlan colours were burned on the orders of the Duke of Cumberland. It had been assumed that the chiefs lands had been forfeited for his support of the Young Pretender and the Jacobite cause, but it was ruled that he had been killed before he could be attainted. The chief of the Campbells, the Archibald Campbell, 3rd Duke of Argyll, who although helped crush the Jacobite forces, aided Donald, son of the deceased Maclachlan chief, and helped saved his lands. On 12 February 1747 Donald Maclachlan of that Ilk received a charter for his lands "at the intercession of the Duke of Argyll", though it was considerably unpopular decision at the time, and Maclachlan's estates were "surveyed but afterwards found not to be forfeited".