At the onset of the First World War the regiment was mobilised and was assigned to the newly formed 6th Guards Infantry Brigade of the 3rd Guards Division. The unit remained in this formation for the course of the war. Initially the fusiliers took part in the invasion of neutral Belgium and were involved in the capture of Namur. They were then deployed to the Eastern Front and fought there in the Battle of the Masurian Lakes. After suffering heavy losses at Brzeziny the remaining members of the regiment had to be gathered into a battalion. On 1 December the unit was regrouped into 2 battalions of 3 companies each. From 22 December the battalions were reorganised into four companies each. In January 1915 the IIIrd Battalion was reformed and the regiment redeployed at the end of that month to the Carpathians. They took part in the months that followed in trench warfare at Zwinin, the ridge finally being taken in April. After further fighting on the Eastern Front the regiment was sent to the West in April 1916, taking part in trench warfare in the Champagne and on the Yser, and participating in the Battle of the Somme. From September to November 1916 it deployed again briefly to the Eastern Front before returning to the West and engaging in trench warfare in Lorraine (region). Here, in December 1916, the regiment was reinforced by a 2nd and 3rd MG company. 1917 saw the unit engaged during the battles of Arras, Passchendaele and Cambrai. At the start of the 1918 German Spring Offensive the fusiliers suffered heavy casualties at Beaumetz and subsequently formed itself into 2 battalions of 3 companies each. On 5 April the regiment was reorganised into 3 battalions again and joined on 14 September 1918 by a MW company.