Cleopatra VII, the last ruler of Ptolemaic Egypt, died on either 10 or 12 August, 30 BC, in Alexandria, when she was 39 years old. According to popular belief, Cleopatra killed herself by allowing an asp (Egyptian cobra) to bite her, but according to the Roman-era writers Strabo, Plutarch, and Cassius Dio, Cleopatra poisoned herself using either a toxic ointment or by introducing the poison with a sharp implement such as a hairpin. Modern scholars debate the validity of ancient reports involving snakebites as the cause of death and whether she was murdered. Some academics hypothesize that her Roman political rival Octavian forced her to kill herself in a manner of her choosing. The location of Cleopatra's tomb is unknown. It was recorded that Octavian allowed for her and her husband, the Roman politician and general Mark Antony, who stabbed himself with a sword, to be buried together properly.

Cleopatra's death effectively ended the final war of the Roman Republic between the remaining triumvirs Octavian and Antony, in which Cleopatra aligned herself with Antony, father to three of her children. Antony and Cleopatra fled to Egypt following their loss at the 31 BC Battle of Actium in Roman Greece, after which Octavian invaded Egypt and defeated their forces. Committing suicide allowed her to avoid the humiliation of being paraded as a prisoner in a Roman triumph celebrating the military victories of Octavian, who would become Rome's first emperor in 27 BC and be known as Augustus. Octavian had Cleopatra's son Caesarion (also known as Ptolemy XV), rival heir of Julius Caesar, killed in Egypt but spared her children with Antony and brought them to Rome. Cleopatra's death marked the end of the Hellenistic period and Ptolemaic rule of Egypt, as well as the beginning of Roman Egypt, which became a province of the Roman Empire.

The death of Cleopatra has been depicted in various works of art throughout history. These include the visual, literary, and performance arts, ranging from sculptures and paintings to poetry and plays, as well as modern films. Cleopatra featured prominently in the prose and poetry of ancient Latin literature. While surviving ancient Roman depictions of her death in visual arts are rare, Medieval, Renaissance, Baroque, and Modern works are numerous. Ancient Greco-Roman sculptures such as the Esquiline Venus and Sleeping Ariadne served as inspirations for later artworks portraying her death, universally involving the snakebite of an asp. Cleopatra's death has evoked themes of eroticism and sexuality in works that include paintings, plays, and films, especially from the Victorian era. Modern works depicting Cleopatra's death include Neoclassical sculpture, Orientalist painting, and cinema.

Following the First Triumvirate and assassination of Julius Caesar in 44 BC, the Roman statesmen Octavian, Mark Antony, and Aemilius Lepidus were elected as triumvirs to bring Caesar's assassins to justice, forming the Second Triumvirate. With Lepidus marginalized in Africa and eventually placed under house arrest by Octavian, the two remaining triumvirs divided control over the Roman world between the Greek East and Latin West, Antony taking the former and Octavian the latter. Cleopatra VII of Ptolemaic Egypt, a pharaoh of Macedonian Greek descent who ruled from Alexandria, had an extramarital affair with Julius Caesar that produced a son and eventual Ptolemaic co-ruler Caesarion. After Caesar's death she developed a relationship with Antony.

With encouragement from Cleopatra, Antony officially divorced Octavian's sister Octavia Minor in 32 BC. It is likely he had already married Cleopatra during the Donations of Alexandria in 34 BC. Antony's divorce from Octavia, Octavian's public revelation of Antony's will outlining Cleopatra's ambitions for Roman territory in the Donations of Alexandria and her continued illegal military support for a Roman citizen currently without an elected office convinced the Roman Senate, now under Octavian's control, to declare war on Cleopatra.

Following their defeat in the naval Battle of Actium at the Ambracian Gulf of Greece in 31 BC, Cleopatra and Antony retreated to Egypt to recuperate and prepare for an assault by Octavian, whose forces grew larger with the surrender of many of Antony's officers and soldiers in Greece. After a long period of failed negotiations, Octavian's forces invaded Egypt early in 30 BC. While Octavian captured Pelousion near the eastern borders of Ptolemaic Egypt, his officer Cornelius Gallus marched from Cyrene and captured Paraitonion to the west. Although Antony scored a small victory over Octavian's worn out troops as they approached Alexandria's hippodrome on 1 August, 30 BC, his naval fleet and cavalry defected soon afterward.

With Octavian's forces in Alexandria, Cleopatra withdrew to her tomb with her closest attendants and had a message sent to Antony that she had died by suicide. Antony ordered his slave Eros to kill him, but instead, Eros killed himself with his sword. In despair, Antony stabbed himself through the stomach with a sword, inflicting a fatal wound. In Plutarch's telling, Antony was still alive as he was carried into Cleopatra's tomb, telling her in his dying words that he would die honorably and that she could trust a certain Gaius Proculeius on Octavian's side to treat her well. The same Proculeius used a ladder to breach a window of Cleopatra's tomb and detain her inside before she could have a chance to burn herself to death along with her vast treasure. Cleopatra was allowed to embalm Antony's body before she was forcefully escorted to the palace, where she eventually met with Octavian, who had also detained three of her children: Alexander Helios, Cleopatra Selene II, and Ptolemy Philadelphus.

As related by Livy, in her meeting with Octavian, Cleopatra told him candidly, "I will not be led in a triumph" (Ancient Greek: οὐ θριαμβεύσομαι, romanized: ou thriambéusomai), but Octavian only gave the cryptic answer that her life would be spared. He did not offer her any specific details about his plans for Egypt or her royal family. After a spy informed Cleopatra that Octavian intended to bring her back to Rome to be paraded as a prisoner in his triumph, she avoided this humiliation by taking her own life. Plutarch elaborates on how Cleopatra approached her suicide in an almost ritual process that involved bathing and then having a fine meal including figs brought to her in a basket.

Plutarch writes that Octavian ordered his freedman Epaphroditus to guard her and prevent a suicide attempt, but Cleopatra and her handmaidens were able to deceive him and kill themselves nonetheless. When Octavian received a note from Cleopatra requesting that she be buried next to Antony, he had his messengers rush to her. The servant broke down her door but was too late. Plutarch states that she was found with her handmaiden, Iras, dying at her feet and Charmion adjusting Cleopatra's diadem before she herself fell. It is unclear from primary sources if their suicides took place within the palace or inside Cleopatra's tomb. Cassius Dio claims that Octavian called on trained snake charmers of the Psylli tribe of Ancient Libya to attempt an oral venom extraction and revival of Cleopatra, but their efforts failed. Although Octavian was outraged by these events and "was robbed of the full splendor of his victory" according to Cassius Dio, he had Cleopatra interred next to Antony in their tomb as requested, and also gave Iras and Charmion proper burials.

There are no surviving records indicating an exact date of Cleopatra's death. Theodore Cressy Skeat deduced that she died on 12 August 30 BC, on the basis of contemporary records of fixed events along with cross examination of historical sources. His supposition is supported by Stanley M. Burstein, James Grout, and Aidan Dodson and Dyan Hilton, although the latter are more cautious by qualifying it was circa 12 August. An alternative date of 10 August 30 BC is supported by scholars such as Duane W. Roller, Joann Fletcher, and Jaynie Anderson.

Cleopatra's personal physician Olympos, cited by Plutarch, mentioned neither a cause of death nor an asp bite or Egyptian cobra. Strabo, who provides the earliest known historical account, believed that Cleopatra died by suicide either by asp bite or poisonous ointment. Plutarch mentions the tale of the asp brought to her in a basket of figs, although he offers other alternatives for her cause of death, such as use of a hollow implement (Greek: κνηστίς, romanized: knestis), perhaps a hairpin, which she used to scratch open the skin and introduce the toxin. According to Cassius Dio small puncture wounds were found on Cleopatra's arm, but he echoed the claim by Plutarch that nobody knew the true cause of her death. Dio mentioned the claim of the asp and even suggested use of a needle (Greek: βελόνη, romanized: belone), possibly from a hairpin, which would seem to corroborate Plutarch's account. Other contemporary historians such as Florus and Velleius Paterculus supported the asp bite version. Roman physician Galen mentioned the asp story, but he advances a version where Cleopatra bit her own arm and introduced venom brought in a container. Suetonius relayed the story of the asp but expressed doubt about its validity.

The cause of Cleopatra's death was rarely mentioned and debated in early modern scholarship. The encyclopedic writer Thomas Browne, in his 1646 Pseudodoxia Epidemica, explained that it was uncertain how Cleopatra had died and that artistic depictions of small snakes biting her failed to accurately show the large size of the "land asp". In 1717 the anatomist Giovanni Battista Morgagni maintained a brief, recreational literary correspondence with the papal physician Giovanni Maria Lancisi about the queen's cause of death, as referenced in Morgagni's 1761 De Sedibus and published as a series of epistles in his 1764 Opera omnia. Morgagni argued that Cleopatra was likely killed by a snakebite and contested Lancisi's suggestion that consumption of venom was more plausible, noting that no ancient Greco-Roman authors had mentioned her drinking it. Lancisi rebutted by arguing that accounts offered by Roman poets were unreliable since they often exaggerated events. In his literary memoirs published in 1777, the physician Jean Goulin supported Morgagni's argument of the snakebite being the most probable cause of death.

Modern scholars have also cast doubt on the story of the venomous snakebite as the cause of death. Roller notes the prominence of snakes in Egyptian mythology while also asserting that no surviving historical account discusses the difficulty of smuggling a large Egyptian cobra into Cleopatra's chambers and then having it behave as intended. Roller also claims the venom is only fatal if injected into a vital area of the body. Egyptologist Wilhelm Spiegelberg (1870–1930) argued that Cleopatra's choice of suicide by asp bite was one that befitted her royal status, the asp representing the uraeus, sacred serpent of the ancient Egyptian sun god Ra. Robert A. Gurval, Associate Professor of Classics at UCLA, points out that the Athenian strategos Demetrios of Phaleron (c. 350 – c. 280 BC), confined by Ptolemy II Philadelphus in Egypt, died by suicide by asp bite in a "curiously similar" manner, one that also demonstrated that it was not exclusive to Egyptian royalty. Gurval notes that the bite of an Egyptian cobra contains around 175–300 mg of neurotoxin, lethal to humans with only 15–20 mg, although death would not have been immediate as victims usually stay alive for several hours. François Pieter Retief, retired lecturer and dean of medicine at the University of the Free State, and Louise Cilliers, honorary research fellow at their Department of Greek, Latin and Classical Studies, argue that a large snake would not have fit into a basket of figs and it was more likely that poisoning would have so rapidly killed the three adult women, Cleopatra and her handmaidens Charmion and Iras. Noting the example of Cleopatra's hairpin, Cilliers and Retief also highlight how other ancient figures poisoned themselves in similar ways, including Demosthenes, Hannibal, and Mithridates VI of Pontus.

According to Gregory Tsoucalas, lecturer in the history of medicine at the Democritus University of Thrace, and Markos Sgantzos, Associate Professor of Anatomy at the University of Thessaly, evidence suggests that Octavian ordered the poisoning of Cleopatra. In Murder of Cleopatra, the criminal profiler Pat Brown argues that Cleopatra was murdered and the details of it were covered up by Roman authorities. Claims that she was murdered contradict the majority of primary sources that report her cause of death as suicide. Historian Patricia Southern speculates that Octavian could have possibly allowed Cleopatra to choose the manner of her death instead of executing her. Grout writes that Octavian may have wanted to avoid the sort of sympathy espoused for Cleopatra's younger sister Arsinoe IV when she was paraded in chains but spared during Julius Caesar's triumph. Octavian perhaps permitted Cleopatra to die by her own hand after considering the political issues that could have risen from the murder of a queen whose statue had been erected in the Temple of Venus Genetrix by his adoptive father. An alternative theory emerged in 1888 when Ambroise Viaud Grand Marais suggested Cleopatra had died of carbon monoxide poisoning.

During her final days, Cleopatra had Caesarion sent away to Upper Egypt and perhaps planned for him to eventually flee to Nubia, Ethiopia, or India in exile. Caesarion reigned as Ptolemy XV for only eighteen days, when he was captured and executed on Octavian's orders on 29 August, 30 BC. This was done following the advice of the Alexandrian Greek philosopher Arius Didymus, who cautioned that two rival heirs to Julius Caesar could not share the world together.

The deaths of Cleopatra and Caesarion marked the end of both the Ptolemaic dynasty's rule of Egypt and the Hellenistic period, which had lasted since the reign of Alexander the Great (r. 336–323 BC). Egypt became a province of the newly established Roman Empire, with Octavian renamed in 27 BC as Augustus, the first Roman emperor, ruling with the facade of a Roman Republic. Roller affirms that Caesarion's alleged reign was "essentially a fiction" invented by chroniclers of Egypt, such as Clement of Alexandria in his Stromata, to explain the gap between Cleopatra's death and the induction of Egypt as a Roman province directly ruled by Octavian as pharaoh of Egypt. Antony's three children with Cleopatra were spared and sent to Rome; their daughter Cleopatra Selene II eventually married Juba II of Mauretania.