In the later part of the Second Earth/ZAFT War, ZAFT introduces two new advanced mobile suits: the ZGMF-X666S Legend Gundam and ZGMF-X42S Destiny Gundam. The Destiny Gundam, designed as a multiple combat role mobile suit, combines the weaponry of several of the Silhouette packs used by the ZGMF-X56S Impulse Gundam. During the design phase, early versions of the Destiny Gundam's weapons are tested in the ZGMF-X56S/θ Destiny Impulse. However, the Destiny Gundam is more than just a combination of Impulse Gundam Silhouette packs, as it introduces several new technologies. The Destiny Gundam uses a hyper deuterion nuclear reactor to power its systems. This new design stores power in deuterion form, providing a continuous deuterion charge and, in theory, an endless power supply. However, it is possible for the suit's power to be expended before the reactor can replenish it. Using a variant of the "Voiture Lumiere" propulsion system of the GSX-401FW Stargazer, the Destiny Gundam can generate a pair of "wings of light," allowing for high-speed movement. During this high speed movement, the wings of light scatter Mirage Colloid particles to create afterimages of the suit in the surrounding area. The Destiny Gundam is also equipped with a pair of "Solidus Fulgor" beam shield generators, which are also used by the Legend Gundam. A standard shield can also be equipped, but is rarely used. The Destiny Gundam's many armaments include a beam rifle, head vulcan guns, a pair of beam boomerangs (which double as beam sabers), hand beam cannons, an anti-ship sword and a long-range beam cannon.

The Destiny Gundam is assigned to ace pilot Shinn Asuka in C.E. 74 by PLANT Supreme Council Chairman Gilbert Durandal after the completion of Operation Angel Down, where Shinn destroys Kira Yamato's ZGMF-X10A Freedom Gundam. Shinn's first use of the Destiny Gundam involves a difficult moral choice: shooting down comrades Athrun Zala and Meyrin Hawke, who defect from ZAFT and escape from the Gibraltar base in a ZGMF-2000 GOUF Ignited. The Destiny Gundam makes its true combat debut in Operation Ragnarok, the ZAFT assault on the Earth Alliance's Heavens Base headquarters. During the battle, Shinn, along with Legend Gundam pilot Rey Za Burrel and Impulse Gundam pilot Lunamaria Hawke, destroy five GFAS-X1 Destroy Gundam units guarding the base, leading to a ZAFT victory. When Logos leader Lord Djibril escapes to the Orb Union, Shinn participates in Operation Fury and engages Kira's ZGMF-X20A Strike Freedom Gundam and Athrun's ZGMF-X19A ∞ Justice Gundam. Soon after, Djibril escapes again to space and fires the Requiem cannon at the PLANTs. Under new orders, the battleship Minerva heads to space and launches an attack on the Alliance's Daedalus lunar base. During the battle, Shinn raids the base's dock and singlehandedly destroys several battleships. Later, when an Orb space fleet attacks ZAFT to seize control of Requiem, Shinn once again fights Kira and Athrun. In the end, the Destiny Gundam is heavily damaged by Athrun and crashes onto the Moon's surface. Soon after, the death of Durandal and the destruction of the space fortress Messiah mark the end of the war.