The novel opens with a recounting of Dr. Catherine Elizabeth Halsey and Lieutenant Keyes' trip to a human colony world (Eridanus 2) where they first meet John, a 6 year old child who they will subsequently enroll in the SPARTAN II program, a secret experiment aimed at creating a force of super soldiers from conscripted children who possess certain genetic markers. The story then moves on with a description of the brutal military training and indoctrination to which John-117 (the children are referred to only by their first name and the original SPARTAN project specimen number they were assigned during initial screening) and the rest of the kids are subjected. During this time John grows from a competitive young boy to the respected leader of the SPARTANs. At the age of 14, John and his teammates undergo biological and cybernetic enhancements that turn them into highly efficient and lethal soldiers; however, out of the original 75 candidates, only 33 survive the process. 30 die as a direct result of the surgery and 12 suffer debilitating side-effects. Later, after their first real successful combat operation, the SPARTANs receive the MJOLNIR combat armor which further enhances their faculties, making them the best soldiers humanity has to offer.

Following these events the reader is introduced to the Covenant and their initial attacks against the outlying human colonies (such as Harvest and Jericho). The SPARTANs spread up along the front to fight the aliens, but humanity's struggle seems desperate as colony after colony is destroyed by the technologically superior Covenant. Shortly after all SPARTANs are re-united to prepare for a secret mission behind enemy lines, the Covenant launch a large scale assault which leads to the destruction of Reach, the planet where the SPARTANs' training center was located and which was as much as a home world for them. The fall of Reach is a notable event in human history because it was the most heavily fortified planet of the UNSC, rivaled only by the now fortified, Earth itself.


The novel ends with an expanded version of the prologue to the original game and the escape of Master Chief John-117 aboard the ship Pillar of Autumn. The vessel follows a "randomized" slipspace vector which leads to the discovery of the Halo installation. This vector is later revealed to have been quickly generated from some Forerunner hieroglyphs by the ship's AI Cortana. While the first Halo game made the Master Chief look like he was the only SPARTAN who survived the destruction of Reach, the book reveals that another SPARTAN II named Linda-058 was placed in cryostasis on board the Pillar of Autumn, neither dead nor alive, after she was gravely wounded during a raid onboard one of Reach space stations.

The novel is the first of a series of six books based around the Halo universe. The second book, Halo: The Flood, written by William C. Dietz, is a novelization of Halo: Combat Evolved. Halo: First Strike, written by Eric Nylund, is a sequel to the original game and a prequel to Halo 2. The sequel to First Strike is Halo: Ghosts of Onyx, also by Eric Nylund. Two more unnamed novels are currently being written.