Soon after 1738, work was started to establish a seaport in the little bay of Le Barachois, on the eastern side of the Saint-Denis River, to replace the port of Saint-Paul, but its site did not offer a safe haven, due to unpredictable winds and tides, as well as frequent high surf which forced ships to unload their cargo in the open roadstead away from the shore, from where it was carried to the shore with the use of a mobile pier.

Improvements in the 19th century resulted in the construction of a small artificial harbor where surf boats in charge of unloading cargo from larger ships could be protected from winds and swells, but it was regularly damaged by cyclones.

Eventually it was replaced by a new and much larger artificial harbor built on the northwest coast of La Réunion in the 1880s, in today's commune of Le Port, 15 kilometres (9.3 mi) from Saint-Denis.

On 6 April 1815, after the Treaty of Paris, the British officially restored Bourbon Island to France during a ceremony held on the main square of Saint-Denis.

Later in October 1815, as news of Napoleon's return to France had arrived in the Indian Ocean, a British fleet from Mauritius presented itself in front of St Denis, asking the French governor of Bourbon Island to surrender the colony to His Britannic Majesty.

The authorities reacted quickly as soon as the disease was discovered in town by isolating sick people, establishing a military cordon sanitaire, and evacuating the rest of the population from the city.

In 1847, the return to Bourbon Island of the Catholic Apostolic Vice-Prefect of the island, Alexandre Monnet, an abolitionist who had worked for the evangelization of Bourbon's Black slaves and was returning from a trip to Europe where he had been celebrated in Paris and Rome for his work in favor of Black slaves, triggered two days of protests in Saint-Denis among the White colonists, who insulted the Apostolic Vice-Prefect without governor Joseph Graëb [fr] intervening to stop the turmoil.

On 18 October 1848 the new Commissioner of the Republic, Sarda Garriga, sent from Paris to replace governor Graëb, announced in Saint-Denis the abolition of slavery in Réunion Island, effective on 20 December 1848.

The rumor led to five days of anti-clerical riots in the city in November-December 1868, with crowds of up to 2,000 gathering in front of the bishop's palace, shouting "Down with La Malle!

The Moroccan rebel leader Abd el-Krim, founder of the Republic of the Rif, was also exiled to Réunion in 1926 after his surrender to French troops, and he lived in Saint-Denis until 1929, before moving to Les Trois-Bassins.

On 10 April 1940 the last public execution in Réunion took place at dawn on that square at the Barachois: two men were guillotined for the savage murder of a 78 year-old female shopkeeper in 1937.

After the successful British landing in Vichy-held Madagascar, and faced with the impossibility to defend Réunion's coastline, governor Aubert on 27 September 1942 decided to declare Saint-Denis an open city and retreat to Hell-Bourg, in the interior of the island.

On 28 November the Free French Naval Forces (FNFL) destroyer Léopard, sailing from Mauritius, arrived off Saint-Denis and landed troops unopposed.

The June 1946 French legislative election was marked by political violence in Réunion, opposing Communist militants and the Christian-democratic Popular Republican Movement (MRP), which had both emerged from the underground resistance during Vichy rule over the island (1940–1942).

Found guilty by the criminal court of Lyon (where the trial had been relocated in order to calm tensions in Réunion), he was granted amnesty in 1953 by the French government.

In 1957, a large modern hospital was opened in Saint-Denis, the Centre hospitalier Félix-Guyon [fr], one of the results of the transformation of the colony into an overseas department in 1946.

Paul Vergès, who was the Communist candidate to become mayor of Saint-Denis, was beaten by Gendarmerie forces during clashes in the streets and left unconscious on the pavement.

Yet in July 1959, Charles de Gaulle, president of France, received a warm welcome on his arrival to Saint-Denis, the first visit by a French head of state since the foundation of the city.

In the countryside, people often resided in huts with bare earth floor, and the housing situation in the city was getting worse every year with the now rapidly growing population.

After stepping down as prime minister in 1962 following the independence of French Algeria (to which he had been opposed), he was determined to prevent the same fate in Réunion, and decided to stand in the 1st constituency of Réunion by-election to the National Assembly in the beginning of 1963 (after the results of the 1962 French legislative election in that constituency, which the mayor of Saint-Denis Gabriel Macé had won, were invalidated by the Constitutional Council due to renewed electoral fraud).

In 1964, the French National Assembly voted the so-called 'Debré Law' (named after its promoter) that facilitated land expropriation and slum clearance in France's urban areas.

In August 1967 the first nonstop commercial flights between Saint-Denis and Paris (operated by Air France's Boeing 707) were launched after the lengthening and modernization of Gillot Airport's runway.

Télé Free Dom had been broadcasting from its studios in Saint-Denis without a license for more than 4 years when CSA, France's electronic media regulatory authority, ordered it to cease operations.

Despite protests from its viewers incited by the founder and owner of Télé Free Dom, a metropolitan Frenchman, the French government instructed the prefect of Réunion to seize the transmitter of the TV station on 24 February 1991.

A month of riots throughout the city ensued after Télé Free Dom went off air, with their epicenter in the large projects of Le Chaudron built in the 1960s and 1970s.

Eight looters died on the night of 25–26 February 1991, trapped inside a burning furniture store, which led to a temporary lull in the riots, but they soon erupted again in March.

The city includes some of the island's mountains, with a peak elevation of 2,276 meters (7,467 ft) within the metro area, which begins at sea level at the coast line.

On 15 March 2022 an aerial tramway, named Papang, started operating, stretching 2.7 km (approximately 1.67 mi) and serving 5 stations between the neighbourhoods of Le Chaudron and Bois-de-Nèfles.

[24] The island began organizing to be a digital hub for nearby African nations, relying on its two undersea cables for good internet connections.

Prince Bảo Vàng of Vietnam (also known as Yves Claude Vinh San) the son of Emperor Duy Tân, was born and resided in Saint-Denis, Réunion for his final years.