Leblanc was born in Rouen, Normandy. After studying in several countries and dropping out of law school, he settled in Paris and began to write fiction, both short crime stories and longer novels; his novels, heavily influenced by writers like Gustave Flaubert and Guy de Maupassant, were critically admired but met with little commercial success.

Leblanc was largely considered little more than a writer of short stories for various French periodicals when the first Arsène Lupin story appeared in a series of short stories serialized in the magazine Je Sais Tout, starting in No. 6, dated 15 July 1905. Clearly created at editorial request under the influence of, and in reaction to, the wildly successful Sherlock Holmes stories, the roguish and glamorous Lupin was a surprise success and Leblanc's fame and fortune beckoned. In total, Leblanc went on to write twenty-one Lupin novels or collections of short stories.

The character of Lupin might have been based by Leblanc on French anarchist Marius Jacob, whose trial made headlines in March 1905; it is also possible that Leblanc had also read Octave Mirbeau's Les 21 jours d'un neurasthénique (1901), which features a gentleman thief named Arthur Lebeau, and seen Octave Mirbeau's comedy Scrupules (1902), whose main character is a gentleman thief. It was not influenced by E. W. Hornung's gentleman thief, A.J. Raffles, created in 1899, whom Leblanc had not read.

Some lupinophiles/lupinologists/lupinomaniacs disturbingly but somewhat convincingly argue (André Comte-Sponville, François George in Preuves de l'existence d'Arsène Lupin) that Lupin really existed and that Leblanc was thus his mere historiographer. In this respect they resemble many fans of Arthur Conan Doyle's Sherlock Holmes.

By 1907 Leblanc had graduated to writing full-length Lupin novels, and the reviews and sales were so good that Leblanc effectively dedicated the rest of his career to working on the Lupin stories. Like Conan Doyle, who often appeared embarrassed or hindered by the success of Sherlock Holmes and seemed to regard his success in the field of crime fiction as a detraction from his more "respectable" literary ambitions, Leblanc also appeared to have resented Lupin's success. Several times, he tried to create other characters, such as private eye Jim Barnett, but eventually merged them with Lupin. He continued to pen Lupin tales well into the 1930s.

Leblanc also wrote two notable science fiction novels: Les Trois Yeux (1919) in which a scientist makes televisual contact with three-eyed Venusians, and Le Formidable Evènement (1920), in which an earthquake creates a new landmass between England and France

Leblanc was awarded the Légion d'Honneur for his services to literature, and died in Perpignan in 1941. He was buried in the Montparnasse Cemetery. Georgette Leblanc was his sister.

The character Arsène Lupin III, protagonist of the Japanese manga Lupin III beginning in 1967 was written as the grandson of Arsène Lupin, though without permission from Leblanc's estate. This was later the source of a lawsuit, though the copyright on Leblanc's work has since expired. When the anime version was broadcast in France, the character was renamed Edgar, le détective cambrioleur ("Edgar, the Burglar Detective"). The authors of the various Lupin III properties drew on Leblanc's novels as inspiration, notably the film The Castle of Cagliostro was loosely based on La Comtesse de Cagliostro (The Countess of Cagliostro).