Georges Simenon was born at 26 rue Léopold (now number 24) in Liège to Désiré Simenon and his wife Henriette. Désiré Simenon worked in an accounting office at an insurance company and had married Henriette in April 1902. Although Georges Simenon was born on February 13, 1903 superstition resulted in his birth being registered as having been on the 12th. This story of his birth is recounted at the beginning of his novel Pedigree. The Simenon family traces its origins back to the Limburg region, his mother's family being from Dutch Limburg. One of her more notorious ancestors was Gabriel Brühl, a criminal who preyed on Limbourg from the 1720s until he was hanged, in 1743. Later, Simenon would use Brühl as one of his many pen names. In April 1905, two years after Georges Simenon's birth, the family moved to 3 rue Pasteur (now 25 rue Georges Simenon) in the city's Outremeuse neighborhood. Georges Simenon's brother Christian was born in September 1906 and eventually became their mother's favorite child, much to Georges Simenon's chagrin. Later, in February 1911, the Simenons moved to 53 rue de la Loi, also in the Outremeuse. In this larger home, the Simenons were able to take in lodgers. Typical among them were apprentices and students of various nationalities, giving the young Simenon an important introduction to the wider world; this marked his novels, notably Pedigree and Le Locataire.

At the age of three, Simenon learned to read at the Saint-Julienne nursery school. Then, between 1908 and 1914, he attended the Institut Saint-André. In September 1914, shortly after the beginning of the First World War, he began his studies at the Collège Saint-Louis, a Jesuit high school. In February 1917, the Simenon family moved to a former post office building in the Amercoeur neighborhood. June 1919 saw another move, this time to the rue de l'Enseignement, back in the Outremeuse neighborhood. Using his father's heart condition as a pretext, Simenon decided to put an end to his studies in June 1918, not even taking the Collège Saint-Louis' year-end exams. He subsequently worked a number of very short-term odd jobs.

In January 1919, the sixteen-year-old Simenon took a job at the Gazette de Liège, a newspaper edited by Joseph Demarteau. While Simenon's own beat only covered unimportant human interest stories, it afforded him an opportunity to explore the seamier side of the city, including politics, bars, cheap hotels, but also crime, police investigations, and lectures on police technique by the criminologist Edmond Locard. Simenon's experience at the Gazette also taught him the art of quick editing. Indeed, he wrote more than 150 articles under the pen name "G. Sim."

Simenon's first novel, Au Pont des Arches was written in June 1919 and published in 1921 under his "G. Sim" pseudonym. Writing as "Monsieur Le Coq," he also published more than 800 humorous pieces between November 1919 and December 1922. During this period, Simenon's familiarity with nightlife only increased: prostitutes, drunkenness, and general carousing. The people he rubbed elbows with included anarchists, bohemian artists, and even two future murderers, the latter appearing in his novel Les Trois crimes de mes amis. He also frequented a group of artists known as "La Caque." While not really involved in the group, he did meet his future wife Régine Renchon through it.

Désiré Simenon died in 1922 and this served as the occasion for the author to move to Paris with Régine Renchon (hereafter referred to by her nickname "Tigy"), at first living in the 17th arrondissement, not far from the Boulevard des Batignolles. He became familiar with the city, its bistrots, cheap hotels, bars, and restaurants. More importantly, he also came to know ordinary working-class Parisians. Writing under numerous pseudonyms, his creativity began to pay financial dividends. Simenon and Tigy returned briefly to Liège in March 1923 to marry. Despite his Catholic upbringing, Simenon was not a believer. Tigy came from a thoroughly non-religious family. However, Simenon's mother insisted on a church wedding, forcing Tigy to become a nominal convert, learning the Catholic Church's catechism. Despite their father's lack of religious convictions, all of Simenon's children would be baptized as Catholics. Marriage to Tigy, however, did not prevent Simenon from having liaisons with numerous other women, perhaps most famously, Josephine Baker.

A reporting assignment had Simenon on a lengthy sea voyage in 1928, giving him a taste for boating. In 1929, he decided to have a boat built, the Ostrogoth. Simenon, Tigy, their cook and housekeeper Henriette Liberge, and their dog Olaf lived on board the Ostrogoth, traveling the French canal system. Henriette Liberge, known as "Boule" (literally, "Ball," a reference to her slight pudginess) was romantically involved with Simenon for the next several decades and would remain a close friend of the family, really part of it.

In 1930, the most famous character invented by Simenon, Commissaire Maigret, made his first appearance in a piece in Detective written at Joseph Kessel's request. 1932 saw Simenon travel extensively, sending back reports from Africa, eastern Europe, Turkey, and the Soviet Union. A trip around the world followed in 1934 and 1935. Between 1932 and 1936, Simenon, Tigy, and Boule lived at La Richardière, a 16th century manor house in Marsilly at the Charente-Maritime département. The house is evoked in Simenon's novel Le Testament Donadieu. At the beginning of 1938, he rented the villa Agnès in La Rochelle and then, in August, purchased a farm house in Nieul-sur-Mer (also in the Charente-Maritime), where his and Tigy's only child, Marc, was born in 1939.

Simenon lived in the Vendée during the Second World War. Simenon's conduct during the war is a matter of considerable controversy, with some scholars inclined to view him as having been a collaborator with the Germans while others disagree, viewing Simenon as having been an apolitical man who was essentially an opportunist, but by no means a collaborator. Further confusion stems from the fact that he was denounced as a collaborator by local farmers while at the same time the Gestapo suspected him of being Jewish, apparently conflating the names "Simenon" and "Simon". In any case, Simenon was under investigation at the end of the war because he had negotiated film rights of his books with German studios during the occupation and in 1950 was sentenced to a five-year period during which he was forbidden to publish any new work. This sentence, however, was kept from the public and had little practical effect.

The war years did see Simenon produce a number of important works, including Le Testament Donadieu, Le Voyageur de la Toussaint, and Le Cercle des Mahé. He also conducted important correspondence, most notably with André Gide. Also in the early 1940s, Simenon had a health scare when a local doctor misdiagnosed him with a serious heart condition (a reminder of his father), giving him only months to live. It was also at this time that Tigy finally surprised her husband with Boule. He and Tigy remained married until 1949, but it was now a marriage in name only. Despite Tigy's initial protests, Boule remained with the family.

Simenon escaped questioning in France and in 1945 arrived, along with Tigy and Marc, in North America. He spent several months in Québec, Canada north of Montréal, at Domaine L'Esterel (Ste-Marguerite du Lac Masson), where he lived in a modern style house, and wrote three novels in one of the log cabins (LC5). Boule, due to visa difficulties, was initially unable to join them. During the years he spent in the United States, Simenon regularly visited New York City. He and his family also went on lengthy car trips, traveling from Maine to Florida and then west as far as California. Simenon lived for a short time on Anna Maria Island near Bradenton, Florida before renting a house in Nogales, Arizona, where Boule was finally reunited with him. His novel The Bottom of the Bottle was heavily influenced by his stay in Nogales, Arizona. Although enchanted by the desert, Simenon decided to leave Arizona, and following a stay in California, settled into a large house, Shadow Rock Farm, in Lakeville, Connecticut. This town forms the background for his 1952 novel La Mort de Belle ("The Death of Belle"). While in the United States, Simenon and his son Marc learned to speak English with relative ease, as did Boule. Tigy, however, had a great deal of trouble with the language and pined for a return to Europe.

In the meantime, Simenon had met Denyse Ouimet, a woman seventeen years his junior. Denyse, who was originally from Montréal, met Simenon in New York City in 1945 (she was to be hired as a secretary) and they promptly began an often stormy and unhappy relationship. After resolving numerous legal difficulties, Simenon and Tigy were divorced in 1949. Simenon and Denyse Ouimet were then married in Reno, Nevada in 1950 and eventually had three children, Johnny (born in 1949), Marie-Jo (born in 1953) and Pierre (born in 1959). In accordance with the divorce agreement, Tigy continued to live in close proximity to Simenon and their son Marc, an arrangement that continued until they all returned to Europe in 1955.

Simenon and his family returned to Europe in 1955, first living in France (mainly on the Côte d'Azur) before settling in Switzerland. After living in a rented house in Echandens, he purchased a property in Epalinges, north of Lausanne, where he had an enormous house constructed. Simenon and Denyse Ouimet separated definitively in 1964. Teresa, who had been hired by Simenon as a housekeeper in 1961, had by this time become romantically involved with him and remained his companion for the rest of his life.

His long-troubled daughter Marie-Jo committed suicide in Paris in 1978 at the age of 25, an event that darkened Simenon's later years.

Simenon underwent surgery for a brain tumor in 1984 and made a good recovery. In subsequent years however, his health worsened. He gave his last televised interview in December 1988.

Georges Simenon died in his sleep of natural causes on the night of September 3 or morning of September 4, 1989 in Lausanne.