The 2nd Battalion sailed on the Nile on 14th March 1900, and arrived at the Cape on 3rd April. Along with the 2nd Grenadier Guards, 2nd Scots Guards, and 1st Leinster Regiment, they formed the 16th Brigade under Major General Barrington Campbell, and part of the VIIth Division under General Sir Leslie Rundle. The work of the brigade and of the division is sketched briefly under the 2nd Grenadier Guards.
The East Yorkshire Regiment were present in the action at Biddulphsberg on 29th May 1900, but their losses were not severe.
The battalion was in no other big battle, but had much skirmishing and endless harassing work. In Lord Roberts' final despatch 10 officers and 12 non-commissioned officers and men were mentioned.
Early on 6th June 1901 Major Sladen of the East Yorkshire Regiment with a party of 200 Mounted Infantry captured a laager and 45 prisoners at Graspan, near Reitz. He at once sent back 40 men to communicate with Colonel De Lisle, as he feared attack, and he took up a defensive position. A very determined attempt was shortly made by 500 Boers under De Wet and other commanders to retake the convoy, but the defenders held out till reinforcements arrived about 3 pm. Many gallant deeds by representatives of sundry regiments were 'mentioned'. Major Sladen got promotion. In the Gazette which announced his reward three men of the East Yorkshire were mentioned for gallant work in the Harrismith-Bethlehem district.
The battalion operated in the north-east of the Orange River Colony practically all the time they were in the campaign.
The Mounted Infantry company were in the action at Kaffir's Spruit, in the Eastern Transvaal, on 19th December 1901, and for exceptionally gallant conduct on that occasion 1 officer and 3 non-commissioned officers were mentioned in Lord Kitchener's despatch of 8th March 1902. In his final despatch 5 officers and 9 non-commissioned officers and men of the battalion were mentioned.