The Iroquois was a UNSC destroyer that entered service in 2552 and was assigned to Captain Jacob Keyes. Soon after commissioning, the Iroquois became involved in a conflict with a small contingent of Covenant warships in the Sigma Octanus system, performing was later become known at the Keyes Loop to evade and destroy two Covenant frigates and a destroyer despite facing overwhelming force. A Covenant carrier evaded the skirmish, deploying troops to the surface of Sigma Octanus IV, to which the Iroquois responded by deploying Spartan-IIs to repel the ground forces.
Following the engagement, repair efforts began on the Iroquois, though were not completed before a full-scale Covenant invasion force entered the system en-route for Sigma Octanus IV. The Iroquois, along with a large contingent of UNSC forces engaged the Covenant forces and won the battle in space, a rare victory for the UNSC. During the battle, the Iroquois discovered a Covenant stealth craft in orbit over the planet, retrieving a signal from Covenant ground forces. The Iroquois engaged, ultimately ramming the vessel and destroying it.
In the aftermath of the battle, the Iroquois left the system for repairs at Reach, though was tagged by a Covenant probe, revealing the location of Reach to the Covenant. Once they arrived at their destination, the crew of the Iroquois was reassigned to the UNSC Pillar of Autumn. The fate of the Iroquois afterwards is unknown, though it was likely involved in the Fall of Reach and destroyed.