McDonald moved west into Virginia's interior and entered the military service of the colonial government under Lieutenant Governor Robert Dinwiddie, receiving the rank of captain.

[1][3] McDonald was a lineal descendant of a long line of military heroes of the Clan MacDonell of Glengarry and of Somerled, Lord of the Isles.

[1][2][3] During the Jacobite rising of 1745, McDonald fought as a lieutenant under the command of Charles Edward Stuart in the Battle of Culloden, after which he was "attainted of treason".

[3][11] McDonald moved west into Virginia's interior and entered the military service of the colonial government under Lieutenant Governor Robert Dinwiddie, receiving the rank of captain.

[2][12] Upon his retirement, Governor John Murray, 4th Earl of Dunmore granted McDonald an additional 2,000 acres (8.1 km2) of land, which were surveyed by Hancock Taylor.

McDonald's accounts along with those of other settlers resulted in Lord Dunmore's decision to wage a war against the Native Americans to pacify the frontier lands of western Virginia for continued settlement.

[19] Once the entire force had converged near Wheeling, McDonald and Captain William Crawford directed the construction of Fort Fincastle in July 1774.

[13][18] McDonald's forces continued their march onto the next Wakatomika settlement, where a further ambush ensued resulting in the burning of Shawnee cabins and villages.

[19] McDonald and his forces returned to Wheeling with three Shawnee tribal chiefs as captives, who were then sent on to the colonial Virginia seat of government, Williamsburg.

[18] McDonald completed the expedition, which met its goal of temporarily relieving western Virginia frontier settlements from Native American attack.

[23] In a letter dated January 8, 1775, following his return to Winchester from Williamsburg, McDonald recounted of the war, "all the Country is well pleased with the Governours Expeditions.

[2][7] In March 1777, McDonald received a personal letter from General George Washington appointing him a lieutenant colonel in a battalion of Thruston's Additional Continental Regiment under the command of Colonel Charles Mynn Thruston, a former rector of Cunningham Chapel in present-day Clarke County, Virginia, and a former associate magistrate of the Frederick County court, where he served alongside McDonald.

[9] McDonald died on August 19, 1778, at his home Glengarry near Winchester after receiving an incorrect dosage of the medication potassium antimonyl tartrate.

[3][25][27] An article published in the Winchester Star in 1967 said of McDonald, "fearsome or not, he founded in the Shenandoah Valley a dynasty of military men as distinguished as their forebears had been in the Scottish Highlands.

"[28] In its documentation of Dunmore's War, the Wisconsin Historical Society stated, "McDonald was a man of commanding figure and strong personality and a rigid disciplinarian with his troops.