Pyrrhus was the son of Aeacides and Phthia, a Thessalian woman, and a second cousin of Alexander the Great (via Alexander’s mother, Olympias). He had two sisters: Deidamia and Troias. In 317 BC, when Pyrrhus was only two, his father was dethroned (for supporting Olympias against Cassander). Pyrrhus' family took refuge with Glaukias of the Taulantians, one of the largest Illyrian tribes. Pyrrhus was raised by Beroea, Glaukias's wife and a Molossian of the Aeacidae dynasty.

Glaukias restored Pyrrhus to the throne in 306 BC until the latter was banished again, four years later, by his enemy, Cassander. Thus, he went on to serve as an officer, in the wars of the Diadochi, under his brother-in-law Demetrius Poliorcetes who had married Deidamia. In 298 BC, Pyrrhus was taken hostage to Alexandria, under the terms of a peace treaty made between Demetrius and Ptolemy I Soter. There, he married Ptolemy I's stepdaughter Antigone (a daughter of Berenice I of Egypt from her first husband Philip—respectively, Ptolemy I's wife and a Macedonian noble) and restored his kingdom in Epirus in 297 BC with financial and military aid from Ptolemy I. Pyrrhus had his co-ruler Neoptolemus II of Epirus murdered. In 295 BC, Pyrrhus transferred the capital of his kingdom to Ambrakia (modern Arta). Next, he went to war against his former ally and brother-in-law Demetrius and in 292 BC he invaded Thessaly while Demetrius was besieging Thebes but was repulsed. In 288 BC, Pyrrhus and Lysimachus shared rulership over the kingdom of Macedon until 284 BC when Lysimachus drove Pyrrhus out of the region back into Epirus.

Routes taken against Rome in the Pyrrhic War (280-275 BC).

The Greek city of Tarentum, in southern Italy, fell out with Rome due to a violation of an old treaty that specified Rome was not to send warships into the Tarentine Gulf. In 282 BC, the Romans installed garrisons in the Greek cities of Thurii (on the western end of the Tarentine Gulf), Locri, and Rhegium, and sent warships to Thurii. Although this was designed as a measure against the Italian peoples of Lucania, the Tarentines grew nervous and attacked the Romans in Thurii, driving the Roman garrison from the city and sinking several Roman warships. Tarentum was now faced with a Roman attack and certain defeat, unless they could enlist the aid of greater powers. Rome had already made itself into a major power, and was poised to subdue all the Greek cities in Magna Graecia. The Tarentines asked Pyrrhus to lead their war against the Romans. Pyrrhus was encouraged to aid the Tarentines by the Oracle of Delphi. He recognized the possibility of carving out an empire for himself in Italy. He made an alliance with Ptolemy Keraunos, King of Macedon and his most powerful neighbor, and arrived in Italy in 280 BC.

Pyrrhus entered Italy with an army consisting of 20,000 infantry, 3,000 cavalry, 2,000 archers, 500 slingers, and 20 war elephants in a bid to subdue the Romans. The elephants had been loaned to him by Ptolemy II, who had also promised 9,000 soldiers and a further 50 elephants to defend Epirus while Pyrrhus and his army were away.

Due to his superior cavalry, his elephants and his deadly phalanx infantry, he defeated the Romans, led by Consul Publius Valerius Laevinus, in the Battle of Heraclea in 280 BC, in the Roman province of Lucania. There are conflicting sources about casualties. Hieronymus of Cardia reports the Romans lost about 7,000 while Pyrrhus lost 3,000 soldiers, including many of his best; Dionysius gives a bloodier view of 15,000 Roman dead and 13,000 Epirot. Several tribes, including the Lucanians, Bruttii, Messapians, and the Greek cities of Croton and Locri, joined Pyrrhus. He then offered the Romans a peace treaty which was eventually rejected. Pyrrhus spent the winter in Campania.

When Pyrrhus invaded Apulia (279 BC), the two armies met in the Battle of Asculum, where Pyrrhus won a costly victory. The consul Publius Decius Mus was the Roman commander, and while his able force was ultimately defeated, they managed to almost break the back of Pyrrhus' Epirot army, which guaranteed the security of the city itself. In the end, the Romans had lost 6,000 men and Pyrrhus 3,500 including many officers.  Pyrrhus later famously commented on his victory at Asculum, stating, "If we are victorious in one more battle with the Romans, we shall be utterly ruined".  It is from reports of this semi-legendary event that the term Pyrrhic victory originates.

In 278 BC, Pyrrhus received two offers simultaneously. The Greek cities in Sicily asked him to come and drive out Carthage, which along with Rome was one of the two great powers of the Western Mediterranean. At the same time, the Macedonians, whose King Ptolemy Keraunos had been killed by invading Gauls, asked Pyrrhus to ascend the throne of Macedon. Pyrrhus decided that Sicily offered him a greater opportunity, and transferred his army there.

Soon after landing in Sicily, he lifted the Carthaginian siege of Syracuse in the same year. Pyrrhus was proclaimed king of Sicily. He was already making plans for his son Helenus to inherit the kingdom of Sicily and his other son Alexander to be given Italy. In 277 BC, Pyrrhus captured Eryx, the strongest Carthaginian fortress in Sicily. This prompted the rest of the Carthaginian-controlled cities to defect to Pyrrhus.

In 276 BC, Pyrrhus negotiated with the Carthaginians. Although they were inclined to come to terms with Pyrrhus, supply him money and send him ships once friendly relations were established, he demanded that Carthage abandon all of Sicily and make the Libyan Sea a boundary between themselves and the Greeks. The Greek cities of Sicily opposed making peace with Carthage because the Carthaginians still controlled the powerful fortress of Lilybaeum, on the western end of the island. Pyrrhus eventually gave in to their proposals and broke off the peace negotiations. Pyrrhus' army then began besieging Lilybaeum. For two months he launched unsuccessful assaults on the city, until finally he realized he could not mount an effective siege without blockading it from the sea as well. Pyrrhus then requested manpower and money from the Sicilians in order to construct a powerful fleet. When the Sicilians became unhappy about these contributions he had to resort to compulsory contributions and force to keep them in line. These measures culminated in him proclaiming a military dictatorship of Sicily and installing military garrisons in Sicilian cities.

These actions were deeply unpopular and soon Sicilian opinion became inflamed against him. Pyrrhus had so alienated the Sicilian Greeks that they were willing to make common cause with the Carthaginians. The Carthaginians took heart from this and sent another army against him. This army was promptly defeated. In spite of this victory, Sicily continued to grow increasingly hostile to Pyrrhus, who began to consider abandoning Sicily. At this point, Samnite and Tarentine envoys reached Pyrrhus and informed him that of all the Greek cities in Italy, only Tarentum had not been conquered by Rome. Pyrrhus made his decision and departed from Sicily. As his ship left the island, he turned and, foreshadowing the Punic Wars, said to his companions: "What a wrestling ground we are leaving, my friends, for the Carthaginians and the Romans."  While his army was being transported by ship to mainland Italy, Pyrrhus’ navy was destroyed by the Carthaginians at the Battle of the Strait of Messina, with 98 warships sunk or disabled out of 110.