Regimental increments arrived in France during late 1917 and early 1918. Upon arrival, the 6th Marine Regiment joined the 5th Marine Regiment and the 6th Machine Gun Battalion to form the 4th Brigade, U.S. 2nd Division (Regular), American Expeditionary Force.
The early spring was devoted to training under French tutelage. The "Marine" Brigade entered the trenches of the Toulon Sector near Verdun in March 1918, where it suffered its first combat casualties. The regiment had 33 men killed while in the trenches, most lost when the 74th Company billeting area was gassed on 13 April 1918.The 4th Brigade was ordered to shore up crumbling French lines near Château-Thierry in late May 1918.
The 6th Regiment took up positions southwest of Belleau Wood, then it was ordered to seize the town of Bouresches and to clear the southern half of Belleau Wood itself on 6 June. These attacks were the beginning of a month-long struggle that eventually became a landmark battle for the U.S. Marine Corps. Colonel Catlin was severely wounded not long after the first waves went over the top; his replacement was Lieutenant Colonel Harry Lee, who would command the regiment for the rest of the war. Gunnery Sergeant Fred W. Stockham voluntarily gave up his own gas mask to a platoonmate and was later awarded a posthumous Medal of Honor for that action. Regimental dentist Weedon Osborne was also awarded a posthumous Navy Medal of Honor.
Regimental losses in this sector were 2,143 over 40 days. In recognition of the "brilliant courage, vigor, spirit, and tenacity of the Marines", the French government awarded Marine units at Belleau Wood the Croix de guerre with Palm and renamed Belleau Wood "Bois de la Brigade de Marine."