Gundam F-91 takes place in U.C. 0123, 30 years after the final battle between Amuro and Char in Char's Counterattack. The colony Frontier IV, on the far end of the Earth sphere is attacked by the Crossbone Vanguard, a mysterious military organization with goals similar to those of the Neo-Zeon. In the midst of the chaos, high school students Seabrook Arno and Cecily Fairchild manage to gather a dozen schoolchildren and attempt to escape the colony. However, before they can get away Cecily is captured and turned over to the Vanguard. Seabrook fails to save her and is shot. His friends take him and leave the colony, leaving Cecily behind.
Cecily is introduced to Korozo, a commanding officer in the Crossbone Vanguard who wears an iron mask. Furthermore, Korozo claims to be Cecily's father. Korozo introduces Cecily to her grandfather, the leader of the Crossbone Vanguard, who tries to convince her to join them. Cecily is dazed by the events.
Meanwhile, Seabrook and his friends run into the EMF's training warship, the Space Ark, in the bordering colony of Frontier I. The crew of the Space Ark is busy transforming the ship into a resistance base against the Vanguard. The Space Ark also contains the prototype mobile suit F91, and Seabrook and his friends decide to help the engineers finish the suit and ready it for combat. Eventually Seabrook becomes pilot of the F91 and infiltrates Frontier IV in an attempt to rescue Cecily. However, Cecily has finally accepted her destiny by the time Seabrook finds her and has become a mobile suit pilot with the Crossbone Vanguard. Cecily tells Seabrook that she cannot leave yet, and helps him to escape. Seabrook regretfully returns to the Space Ark.
The EMF and the Crossbone Vanguard clash several more times, and during these battles Seabrook's and Cecily's New Type powers start to emerge. Eventually, Seabrook convinces Cecily to leave the Vanguard and join the crew of the Space Ark. As the EMF forces start to gain the upper hand in their war with the Vanguard, Korozo decides to use one of his final weapons. Korozo releases the "bugs" into Frontier I in an attempt to destroy the F91 and the Space Ark. The "bugs" are modified bits that seek out and destroy anything they find. Appalled by the mass destruction and death the bugs cause, Seabrook and Cecily use their New Type powers to destroy them and then go after Korozo in his Mobile Armor. Cecily's mobile suit is destroyed by Korozo, and Cecily herself is lost in space. An enrages Seabrook uses the F91 and his New Type powers to destroy Korozo's Mobile Armor, killing Korozo in the process. Eventually Seabrook manages to find Cecily using the F91, and as the two embrace the Crossbone Vanguard retreats to regroup and prepare for future battles.