In late April 1898, the regiment was assembled in its entirety for the first time in many years at Camp Thomas, Georgia. It did not stay there long and was moved to Tampa, Florida, to join Major General William R. Shafter’s V Army Corps in the impending expedition to Cuba. The regiment embarked on 8 June and arrived at Siboney, Cuba, on the 22nd. Over the next 8 days it moved with the corps slowly toward Shafter’s main objective, the port of Santiago. On the morning of 1 July 1898, the troops of the 16th Infantry, as part of the 1st Division, moved into line for an attack on the heights above Santiago.
The 1st Brigade, commanded by Brigadier General Hamilton S. Hawkins, was assigned as its objective a block house on what was called San Juan Hill. In the ensuing attack, it was the 16th Infantry that captured the blockhouse and whose colors were first on the hill. Over the next two and a half weeks, the troops of the V Corps dug in around the heights looking down on the city and laid siege until the Spanish surrendered. While Spanish bullets were responsible for many of the regiment’s killed and wounded, it was Yellow Fever and other maladies that began to rapidly deplete the strength of the U.S. forces. As a result, President McKinley ordered the troops home and the regiment arrived at Montauk Point, New York, on 15 August 1898.