Dr. Ryland Grace is a junior high school science teacher and former molecular biologist from San Francisco. He finds himself as the sole surviving astronaut on a desperate interstellar mission to save Earth from a sun-eating alien microbe called Astrophage. Relying on his sarcastic humor and extensive scientific knowledge, he works to solve the crisis while his memories of how he joined the project slowly return.

Rocky is an Eridian, a dog-sized, spider-like extraterrestrial whose body is made of hard mineral skin. He relies on highly developed sonar instead of sight and communicates through musical chords. As the brilliant sole surviving engineer of his own species' ship, he partners with Grace to investigate how to save both of their home planets from Astrophage.

Eva Stratt is the authoritarian leader of Project Hail Mary, granted absolute global power and legal immunity by the United Nations. Formerly with the European Space Agency, she is utterly single-minded in her pursuit of a solution to the Astrophage crisis. She operates with a cold, rational assessment of risk and is willing to make any sacrifice to ensure humanity's survival.

Yáo Li-Jie is the stern and disciplined commander of the Hail Mary mission. Driven by a deep sense of honor, he assumes ultimate responsibility for the well-being of his crew. He brings military precision and leadership to the high-stakes international team.

Olesya Ilyukhina is the Russian engineer assigned to the Hail Mary mission. Rowdy and funny, she often provides comic relief during the tense preparations on Earth. Underneath her humorous exterior lies a highly competent and dedicated professional.

Dr. Lokken is a Norwegian climatologist tasked with designing the Hail Mary spacecraft. She initially clashes with Grace due to his controversial academic past but works diligently to create a ship capable of maintaining a gravity environment for laboratory equipment.

Dmitri Komorov is a Russian scientist responsible for designing the spin drive engine for the Hail Mary. He discovers how to convert Astrophage energy into mass for propulsion, creating the highly volatile system that will power the interstellar journey.

Dr. Lamai is a Thai scientist who developed specialized medical coma technology. Her fully automated system is chosen to keep the Hail Mary crew safely unconscious and preserve resources during the long interstellar flight.

Robert Redell is an incarcerated engineer recruited by Stratt to design a massive solar energy conductor. Motivated by self-interest and profit, his "blackpanel" technology is essential for breeding the massive amounts of Astrophage required for the mission.

Steve Hatch is a professor at the University of British Columbia who designs the "Beetle" data probes. He brings a surprisingly cheerful attitude to the dire project, viewing the Astrophage crisis as a divine opportunity for humanity to harness clean energy.

François Leclerc is a climatologist who predicts the timeline of Earth's impending famine. He is given the heartbreaking task of intentionally triggering global warming to counteract the cooling effects of the Astrophage, a necessity that deeply offends his environmentalist values.

Martin DuBois is the meticulous original science specialist chosen for the Hail Mary crew. He is highly pragmatic, prioritizing risk-averse planning and rigorous research as he prepares for the interstellar journey.

Dr. Annie Shapiro is an expert in DNA research acting as the mission's backup scientist. She is known for her rock-star reputation in the scientific community and forms a close personal bond with her primary counterpart during their rigorous training.