Captain Andrew Del Rio is the commanding officer of the UNSC Infinity, the most technologically-advanced starship ever created by Humans. In 2557, when UNSC scientists discovered a series of coordinates in a signal emanating from a Forerunner artifact on Gamma Halo (Installation 03), the Infinity was sent to investigate, and came upon the Forerunner Shield World Requiem, as well as picking up the garbled distress signal of the drifting hulk of the UNSC Forward Unto Dawn, which had been assumed destroyed, and its passengers - the Master Chief and Cortana - killed in action since 2553.
Despite the best efforts of the Chief and Cortana to warn the approaching ship of the powerful gravity well on Requiem's exterior, the Infinity was caught in its grip and pulled inside, where it made a crash landing on the planet's surface shortly after an ancient Forerunner prisoner, the Didact, was freed by a remnant of Covenant religious extremists, who believed the Didact was a living god.
During the following engagements, Captain Del Rio made several questionable command decisions, including sending out scouting parties while the ship was under attack from a combined force of Covenant and the Didact's synthetic army, known as Prometheans. The sole surviving scouting party, who had been saved by the timely arrival of the Master Chief, had determined the location of the generator that powered the gravity well that kept the Infinity trapped on the surface. After the Master Chief helped the Infinity fight off the invaders, repairs were made and the ship took off again. A campaign was undertaken by the crew of the Infinity, joined by the Master Chief, to destroy this generator and open the door to let them leave.
Unlike the grand majority of Humanity, Del Rio seemed to have very little respect for the Chief and Cortana, who had saved the Human race on multiple occasions, seeing them as "an aging Spartan and a malfunctioning AI", dismissing their advice on numerous occasions and eventually going as far as to openly resent them. When Cortana, who was operating well past the usual seven-year lifespan of UNSC AIs, began to show signs of Rampancy, a form of terminal insanity, he ordered her removed from the Infinity's systems and deleted. When his second-in-command, Thomas Lasky, who deeply respected the Master Chief, hesitated, the Chief removed Cortana from the system himself, but disobeyed Del Rio's orders and brought her with him as he left the Infinity to try and deal with the Didact, who stood as the greatest threat Humanity had faced since the end of the Human-Covenant War, and the destruction of the Flood Gravemind, though Del Rio dismissed this claim.
After the Master Chief abandoned the Infinity, the ship exited Requiem and departed for Earth. The Master Chief and Cortana were unable to prevent the Didact from leaving Requiem by themselves; whether or not they would have succeeded with the backing of the Infinity is debatable, but the ship's presence couldn't have hurt matters.
Andrew Del Rio is not seen again during the Halo 4 campaign. When the Master Chief returns to Earth aboard the Didact's mothership, which is preparing to deploy a Forerunner weapon of mass destruction and annihilate all Human life on the planet, he learns that UNSC Fleet Command was extremely displeased that Captain Del Rio abandoned a legendary hero like the Master Chief on Requiem, and stripped him of his command; Thomas Lasky was then promoted to Captain and given full command of the UNSC Infinity.