As the War continues, Amuro and the White Base crew must make their way toward the Earth Federation Headquarters, Jaburo. On their way they meet several new enemies and face off against impossible odds. They fight in Operation Odessa to relieve the Earth from the clutches of the Zeon forces. Lives are lost, new friendships are made, and discoveries at every corner. Amuro soon learns that he possesses the powers of the mysterious Newtypes.

The story is set in 1955 in Kokuga, Hofu City, Yamaguchi Prefecture. One thousand years ago it was the site of the ancient capital, Suo no Kuni, and traces of the Heian Period (year 794-1185) are passed down to us in the form of ruins and historical place names. The protagonist is Shinko, a third grade elementary school student, who was born and raised in one of the town's venerable families. She is a little girl whose characteristic is a strange curl on her forehead (she calls it her "Mai Mai"), and her love for playing in the fields. On the other hand, her secret joy is to imagine and to daydream about the world of one thousand years ago. Her fantasies travel far into the days of the Heian Period... One day, a girl called Kiiko transfers from Tokyo and enters Shinko's class. This girl from the big city has difficulty feeling at home in this small town, but gradually her friendship with Shinko deepens. Before long, the two of them become engulfed in a strange incident of one thousand years earlier...?!

In an alternate timeline, the world has seemingly achieved peace. Bereft of international conflicts, wars are now waged between private corporations in place of peaceful nations. Yuuichi Kannami, a recent transfer in Area 262, simply does his job as a contracted fighter pilot. However, the more time he spends at his new base, the more mysteries come to light. The Sky Crawlers exhibits this reality through the eyes of Kannami as he endeavors to understand the "Kildren," humans genetically altered to be teenagers forever with faster reflexes, and his predecessor, the ace pilot known as "Teacher." However, what troubles Kannami the most is how all this connects to the base commander, Suito Kusanagi. Area 262 has the answers, but the truth comes with a price the young pilot may not be ready to pay.

In the distant future, humanity is hurtling down a path of ruin. Global environmental destruction caused by chemical contamination, radioactive fallout, and UV rays coming through the patchy ozone layer has lead to deterioration of the human genome.