The 2nd battalion sailed for South Africa in October 1899, and when Lord Methuen arrived in November the 9th Brigade was formed of troops then in Cape Colony. It was composed of the 1st Battalion Northumberland Fusiliers, one-half of the 1st Loyal North Lancashire Regiment, the 2nd Northampton Regiment, and the 2nd King's Own Yorkshire Light Infantry, the other half of the North Lancashire Regiment being shut up in Kimberley. The work of the brigade has been sketched under the 1st Northumberland Fusiliers.
At Belmont, 23rd November 1899, the Northamptonshire Regiment were in the first line, but were fortunate enough to escape without heavy loss. Their casualties were 3 officers and 15 men wounded. At Enslin, 25th November, their losses were trifling.
The battalion was not in the action at Modder River on 28th November, having been detailed to guard the railway.
On 8th December a strong force of Free Staters with three guns attacked two companies of the Northamptonshire Regiment near Graspan, but the attack was successfully driven off.
The 9th Brigade was to some extent broken up in the autumn of 1900. In October, November, and December the Northamptonshire Regiment were part of a column under Major General Douglas which operated in the south-west of the Transvaal.
Early in 1901 the battalion was taken to the Central Transvaal, and along with the Wiltshire Regiment occupied posts on the line between Warm Baths and Pietersburg. The battalion was employed chiefly in this district till the close of the campaign.
Thirteen officers and 12 non-commissioned officers and men were mentioned in Lord Roberts' final despatches. During the second phase of the war a few more commendations were got, and in Lord Kitchener's final despatch 3 officers and 3 non-commissioned officers were mentioned.