The protagonist and narrator of Project Hail Mary, Dr. Ryland Grace grows from a brilliant but combative and emotionally guarded scientist into a devoted friend willing to make the ultimate sacrifice to save all human and Eridian life. Although Grace often distracts himself from upsetting thoughts with humor or scientific calculations, he values feelings and relationships greatly. He is sensitive to the cultural norms of others, both on Earth and with Eridians. He is a devoted teacher whose irreverence makes him popular among his junior high students, and he cares deeply for his students, crew mates, and, later, Rocky. Still, Grace is insecure and resentful over his expulsion from academia in response to his confrontational and controversial paper on extraterrestrial life, and he avoids both professional success and emotional intimacy out of a fear of rejection. Grace is also a talented scientist, with a broad base of general knowledge he humorously attributes to teaching junior high science, but which belies his wide-ranging expertise. However, Grace can be reckless and speculative in his scientific experiments, with results that vary from genius to disastrous, and he is prone to wild hypothesizing that occasionally leads to more trouble.

Throughout the novel, Grace struggles to reconcile his survival instinct with the sacrifices he must make for the good of others.