In mid-March 1720 the port city of Marseille recorded the first confirmed case of bubonic plague linked to an arriving ship, initiating one of the last major urban plague epidemics in Europe. The infection was associated with the ship Grand-Saint-Antoine, which had recently arrived from the Levant carrying cargo and passengers, some of whom were ill. Despite quarantine regulations, bureaucratic and commercial pressures led to the unloading of goods and movement of people, facilitating the spread of Yersinia pestis within the densely populated harbor and adjoining neighborhoods. Marseille was a major Mediterranean commercial hub in the early 18th century, handling trade between southern France, the Ottoman Levant, and North Africa. Authorities maintained a system of maritime quarantine and lazarets (isolation hospitals) intended to prevent the importation of contagious diseases. In 1720 these measures were inconsistently enforced: local merchants resisted long detentions of valuable cargo, and civic officials sometimes prioritized commerce over strict isolation. Contemporary records indicate that ill crew members were boarded and goods removed before an effective isolation could take hold, allowing infected rats and fleas to come ashore and enter local households. The disease spread rapidly through the poorer, more crowded districts, where sanitary conditions and close household contacts amplified transmission. Symptoms—swollen buboes, fever, and high mortality—were recognized by physicians of the period as characteristic of plague, and subsequent investigations and registers documented a sharp rise in deaths. The epidemic in Marseille lasted roughly from 1720 into 1722, with thousands of fatalities in the city and surrounding Provence; mortality estimates vary among sources, reflecting incomplete records and differing methods of enumeration. The Marseille epidemic had broader consequences. The French crown intervened by imposing cordons sanitaires—military-enforced quarantines—intended to prevent the disease’s spread into the interior. Local economy and trade were severely disrupted, and neighboring regions took rigorous precautions to avoid contagion, including closing roads and ports. The crisis stimulated debate about public health governance, quarantine policy, and the balance between commerce and disease prevention. It also reinforced the use of lazarets and strengthened municipal disease surveillance in many Mediterranean ports. Historical accounts of the 1720 Marseille plague draw on municipal registers, notarial records, correspondence, and contemporary medical reports. Precise casualty figures remain uncertain: different contemporary and later sources report varying numbers for deaths in Marseille and Provence. While historians agree that the Grand-Saint-Antoine arrival and failures in quarantine were pivotal factors, the complex interplay of trade, administration, and urban conditions is recognized as the broader context for the resurgence. The Marseille outbreak is often cited by historians as the most significant confirmed reappearance of bubonic plague in early-18th-century Europe and marks a turning point in how authorities sought to manage maritime disease risks. No modern genetic confirmation was available to contemporaries; modern studies of historical plague rely on archaeological and biomolecular analyses from different sites and periods. For the Marseille epidemic, conclusions about cause rely primarily on consistent clinical descriptions, patterns of spread, contemporaneous attribution to plague, and the documented social and administrative failures that permitted introduction and dissemination. Because sources vary and some records are incomplete, elements such as exact death tolls and precise transmission chains remain subject to scholarly analysis and debate.