From time to time, a work of fiction appears that exerts a powerful influence on the culture of the day, generating admiration and imitation alike. After John le Carre published “Tinker, Tailor, Soldier, Spy” in 1974, spy stories about the hunt for a Soviet mole proliferated. Stephen King’s “The Shining” inspired a host of lesser novels that featured paranormal children and such titles as “The Piercing” and “The Suiting,” a phenomenon that serious horror fans referred to as “The Gerunding.” Further back, Robert Traver made what was then an unusual decision: using a real murder trial as the basis of his 1958 novel, “Anatomy of a Murder.” The legal thriller that we know today arose directly from that decision.

Thomas Harris did not invent the serial killer novel, but he elevated it. His best work — for me, that would be the interconnected novels “Red Dragon” and “The Silence of the Lambs” — displays a level of craftsmanship that rarely falters. More than that, these are deeply empathetic books in which horrific acts stand side by side with subtle, sympathetic portraits of the damaged souls who commit them. In Harris’s hands, the roots of incomprehensible violence become shockingly, often heartbreakingly clear.

Harris began his career as a crime writer for the Associated Press in the early 1970s. His debut as a novelist was the 1975 publication of “Black Sunday.” A bestseller in the mode of Frederick Forsyth, it remains the odd man out in Harris’s modest body of work. A novel of terrorism rooted in Middle Eastern politics, it tells of an attack on the Super Bowl by a rogue pilot flying a weaponized Goodyear Blimp. Though a bit dated, it remains a solidly entertaining narrative but gives little hint of the fictional transformation to come.

That transformation began with the appearance in 1981 of “Red Dragon,” a crime novel unlike anything that had come before. Novels dealing with serial killers were certainly nothing new and include Ellery Queen’s “Cat of Many Tails” (1949), Lawrence Sanders’s “The First Deadly Sin” (1973) and Shane Stevens’s masterful “By Reason of Insanity” (1979). “Red Dragon” transcended them all.

The plot is relatively simple. An unknown culprit is murdering entire families in the southern United States. Will Graham, a retired FBI agent with an unusual ability to enter the darkest corners of the human mind, is called in to investigate. Will’s journey takes him into the orbit of two very different murderers: the lost and damaged Francis Dolarhyde, and the brilliant Hannibal Lecter, who has since become one of the great fictional boogeymen of our time. The investigation that follows is one of the most enthralling in modern fiction, and one of the most tragic.

“Red Dragon” was followed seven years later by “The Silence of the Lambs,” in which an FBI trainee, Clarice Starling, finds herself enmeshed in a bizarre relationship with the imprisoned Lecter, who, for reasons of his own, aids her in the search for a rampaging serial killer known as Buffalo Bill.

Thanks in part to Jonathan Demme’s award-winning film, the scenes between the two — seductive, enigmatic, often chilling — have become a lasting part of American popular culture. This book, together with its predecessor, solidified Harris’s place as one of crime fiction’s most significant figures.

Harris would go on to write two more novels featuring Lecter. The first and most ambitious, “Hannibal,” shows us Lecter on the loose, traveling through Europe and America toward a controversial denouement with Clarice Starling. Readers will be debating the ending for a long time to come. “Hannibal Rising” takes us back to World War II, and to the formative events of Hannibal’s youth. Brilliant and problematic, these books are required reading for Harris fans. Still, the core of his achievement — and the primary source of his influence — lies in those remarkable early volumes.

That influence has been pervasive, lending its coloration to an array of films, books and television shows both here and abroad. Aspects of Harris’s fiction — empathetic investigators, cutting-edge forensics, bureaucratic inanity, psychically damaged murderers — are part of the fabric of many contemporary crime dramas.

On television, shows such as “Profiler,” “Touching Evil” and “Wire in the Blood” featured protagonists deeply attuned to the minds and motivations of violent criminals. Shows like “CSI,” with its intense focus on forensic detail, and “Criminal Minds,” with its serial killer of the week and emphasis on psychological profiling, are similarly indebted. In books, a number of gifted writers have absorbed Harris’s influence and produced memorable works of their own. These include America’s Chelsea Cain (the Gretchen Lowell series) and Caleb Carr (“The Alienist,” which, in turn, was adapted for television), Britain’s Val McDermid (The Tony Hill/Carol Jordan novels, which inspired “Wire in the Blood”) and South Africa’s Rennie Airth, whose 1999 historical thriller “River of Darkness” is one of the finest serial killer novels to be published in the years since “The Silence of the Lambs.”

Meanwhile, adaptations of Harris’s books continue to appear. Each of his novels has been filmed at least once. The TV series “Hannibal,” which ended a three-season run in 2015, took the central elements of Harris’s fiction — characters, relationships, criminal investigations — and reconfigured them, providing a wholly new perspective on familiar events.

Harris has even found his way into legitimate theater by way of the off-Broadway musical “Silence!,” a relentlessly silly parody of “The Silence of the Lambs.” (Harris fans take note: If you haven’t witnessed Hannibal Lecter serenade Clarice from behind the bars of his cell or thrilled to the sight of a chorus line wearing floppy lambs’ ears, your life is incomplete.)

Given Harris’s relatively small output, the scope of his influence on popular culture may seem disproportionate. It’s not, though, and anyone taking a fresh look at that body of work will see why. Harris once wrote that “when you are writing a novel, you are not making anything up. It’s all there and you just have to find it.”

The best of Harris’s work, and this includes his latest, long-awaited novel, “Cari Mora,” has just that feeling of absolute, unquestionable reality. Through a combination of elements — a perfectly realized authorial voice, the steady accumulation of terrible details, an empathetic vision of lost and damaged souls — Harris has created a sense of dreadful intimacy that we cannot escape, that forces us to gaze at unthinkable things, and never look away. No one has illuminated this kind of darkness more thoroughly or effectively than Harris. It seems unlikely that anyone ever will.

Bill Sheehan is the author of “At the Foot of the Story Tree: An Inquiry Into the Fiction of Peter Straub.”