The 378th Infantry Regiment was organized at Camp Swift, Texas, on July 15, 1942, and trained through Texas, Louisiana, California, and Pennsylvania before sailing from Boston in August 1944. It landed in France on September 15 with the 95th Infantry Division and entered the Moselle fighting south of Metz. On November 11 the regiment established a bridgehead across the Moselle at Thionville. Its battalions fought for Fort Yutz from November 11 to November 13 and Fort d'Illange on November 14-15, anchoring the division's northern pressure while the 377th held Uckange. The 2nd Battalion's Moselle bridgehead fighting earned a Distinguished Unit Citation. The 378th then attacked the Canrobert line and Feves ridge, took Fort le Feves and nearby high ground, linked with the 377th near Woippy, and entered Metz with the division's assault group.
The regiment joined the late-November drive across the Nied into abandoned Maginot Line defenses, reaching Falck and Dalem before the division met hard resistance on the Saar heights. During the Saar operation it seized ground near Berus, took Pikard, and crossed at Lisdorf into the Ensdorf fight. From December 5 to December 20 the 378th struggled under shellfire in and around Ensdorf before withdrawing to the west bank as the Saarlautern bridgehead was consolidated. After winter service in the Saar sector and Holland, it helped reopen the offensive in March 1945. Driving through Uerdingen, the regiment reached Rheinhausen on March 5 after the Rhine bridges had been destroyed. In April it crossed the Lippe River and Canal in the Ruhr campaign, spent four days clearing Hamm, took Kamen with the 379th, and fought through Dortmund on April 12-13.
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