Publius Scipio was born into one of the great patrician families in Rome; his father, grandfather, and great-grandfather had all been consuls in their day. In 218 BC Scipio's father, also named Publius, held the consulship in one of the most critical years of Rome's history. While with him during a cavalry engagement on the Ticinus, the young Scipio made his first appearance in history: seeing his father wounded and cut off by the enemy, he charged forward and saved him. This anecdote is recorded by the historian Polybius on the authority of Scipio's friend Laelius, and it may well be true.

Of Scipio's boyhood or the date of his marriage to Aemilia, daughter of Aemilius Paullus, consul of 216 who fell at Cannae, nothing is known. He had two sons: Publius, who was debarred by ill health from a public career and who adopted Scipio Africanus the Younger; and Lucius, who became praetor in 174. Scipio's physical appearance is shown on some coins minted at Carthago Nova (Cartagena)—which almost certainly bear his portrait—and also probably on a signet ring found near Naples.

Scipio served as a military tribune at the disastrous Battle of Cannae in 216. He escaped after the defeat to Canusium, where some 4,000 survivors rallied; there he boldly thwarted a plot of some fainthearts to desert Rome. Then in 213 he returned to a civilian career by winning the curule aedileship; the story is told that when the tribunes objected to his candidature because he was under the legal age, he replied “If all the Roman people want to make me aedile, I am old enough.” Soon family and national disaster followed: his father and uncle were defeated and killed in Spain, where the Carthaginians swept forward to the Ebro (211).

In 210 the Romans decided to send reinforcements to Spain, but it is said that no senior general would undertake the task and that young Scipio offered himself as a candidate; at any rate, the Roman people decided to invest him with a command there, although he was technically a privatus (not a magistrate). This grant by the people, to a man who had not been praetor or consul, of a military command outside Italy created an important constitutional precedent. Thus Scipio was given the chance to avenge his father's death in Spain, where he hoped not merely to hold the Carthaginian armies at bay and prevent them sending reinforcements to Hannibal in Italy but to resume his father's offensive policy, to turn back the tide of war, and to drive the enemy out of the peninsula. Such a task must have seemed fantastic in 210, but Scipio had the confidence and ability; it was achieved in the next four years.

From his headquarters at Tarraco (Tarragona) in 209, Scipio suddenly launched a combined military and naval assault on the enemy's headquarters at Carthago Nova (Cartagena), knowing that all three enemy armies in Spain were at least 10 days distant from the city. Helped by a lowering of the water in a lagoon, which exposed the northern wall, he successfully stormed the city. This tidal phenomenon, attributed to the help of Neptune, was perhaps caused by a sudden wind; at any rate, it increased the troops' belief in their commander's divine support. In Carthago Nova he gained stores and supplies, Spanish hostages, the local silver mines, a splendid harbour, and a base for an advance farther south.

After training his army in new tactics, Scipio defeated the Carthaginian commander Hasdrubal Barca at Baecula (Bailen) in Baetica (208); whereas normally the two rear ranks of a Roman army closely supported the front line, Scipio in this battle, under a screen of light troops, divided his main forces, which fell upon the enemy's flanks. When Hasdrubal broke away, ultimately to join his brother Hannibal in Italy, Scipio wisely declined the impossible task of trying to stop him and decided rather to accomplish his mission in Spain—the defeat of the other two Carthaginian armies still there. This he brilliantly achieved in 206 at a battle at Ilipa (Ilipa, Battle of) (Alcalá del Río, near Sevilla), where he held the enemy's main forces while the wings outflanked them. He then secured Gades (Cádiz), thus making Roman control of Spain complete.

Elected consul for 205, Scipio boldly determined to disregard Hannibal in Italy and to strike at Africa. Having beaten down political opposition in the Senate, he crossed to Sicily with an army consisting partly of volunteers. While preparing his troops, he boldly snatched Locri Epizephyrii in the toe of Italy from Hannibal's grasp, though the subsequent misconduct of Pleminius, the man he left in command of the town, gave Scipio's political opponents cause to criticize him. In 204 he landed with perhaps 35,000 men in Africa, where he besieged Utica. Early in 203 he burned the camps of Hasdrubal (son of Gisgo) and his Numidian ally Syphax. Then, sweeping down on the forces that the enemy was trying to muster at the Great Plains on the upper Bagradas (modern Sūq al Khamīs, on the Majardah in Tunisia), he smashed that army by a double outflanking movement.

After his capture of Tunis, the Carthaginians sought peace terms, but Hannibal's subsequent return to Africa led to their renewing the war in 202. Scipio advanced southwestward to join the Numidian prince Masinissa, who was bringing his invaluable cavalry to his support. Then he turned eastward to face Hannibal at the Battle of Zama; his outflanking tactics failed against the master from whom he had learned them, but the issue was decided when the Roman and Numidian cavalry, having broken off their pursuit of the Punic horsemen, fell on the rear of Hannibal's army. Victory was complete, and the long war ended; Scipio granted comparatively lenient terms to Carthage. In honour of his victory he was named Africanus.

In 199 Scipio was censor and became princeps Senatus (the titular head of the Senate). He held this position until his death, the following two pairs of censors having confirmed him in the position. Though he vigorously supported a philhellenic policy, he argued during his second consulship (194) against a complete Roman evacuation of Greece after the ejection of Philip V of Macedonia, fearing that Antiochus III of Syria would invade it; his fear was premature but not unfounded. In 193 he served on an embassy to Africa and perhaps also to the East. After Antiochus had advanced into Greece and had been thrown out by a Roman army, Scipio's brother Lucius was given the command against him, Publius serving as his legate (190); together the brothers crossed to Asia, but Publius was too ill to take a personal part in Lucius' victory over Antiochus at Magnesia (for which Lucius took the name Asiagenus).

Meantime, in Rome, Scipio's political opponents, led by the elder Cato (Cato, Marcus Porcius), launched a series of attacks on the Scipios and their friends. Lucius' command was not prolonged; the generous peace terms that Africanus proposed for Antiochus were harshly modified; the “trials of the Scipios” followed. On the trials the ancient evidence is confusing: in 187 an attack on Lucius for refusing to account for 500 talents received from Antiochus (as war indemnity or personal booty?) was parried, and Africanus himself may have been accused but not condemned in 184. In any case, his influence was shaken, and he withdrew from Rome to Liternum in Campania, where he lived simply, cultivating the fields with his own hands and living on a villa (country farm) of modest size: Seneca later contrasted its small and cold bathroom with the luxurious baths of his own day. He had not long to live, however; embittered and ill, he died in 184 or 183, a virtual exile from his country. He is said to have ordered his burial at Liternum and not in the ungrateful city of Rome, where his family tomb lay outside, on the Appian Way.

Such was Scipio's impact upon the Romans that even during his lifetime legends began to cluster around him: he was regarded as favoured by Fortune or even divinely inspired. Not only did many believe that he had received a promise of help from Neptune in a dream on the night before his assault on Carthago Nova but that he also had a close connection with Jupiter. He used to visit Jupiter's temple on the Capitol at night to commune with the god, and later the story circulated that he was even a son of the god, who had appeared in his mother's bed in the form of a snake.

The historian Polybius thought that this popular view of Scipio was mistaken and argued that Scipio always acted only as the result of reasoned foresight and worked on men's superstitions in a calculating manner. But Polybius himself was a rationalist and has probably underestimated a streak of religious confidence, if not of mysticism, in Scipio's character that impressed so many of his contemporaries with its magnanimity and generosity. Thus, although Polybius had an intense admiration for Scipio, whom he called “almost the most famous man of all time,” the existence of the legend, a unique phenomenon in Rome's history, indicates that Polybius' portrait is too one-sided.

A man of wide sympathies, cultured and magnanimous, Scipio easily won the friendship of such men as Philip, king of Macedonia, and the native princes of Spain and Africa, while he secured the devotion of his own troops. Though essentially a man of action, he may also have been something of a mystic in whom, at any rate, contemporary legend saw a favourite of Jupiter as well as a spiritual descendant of Alexander the Great. One of the greatest soldiers of the ancient world, by his tactical reforms and strategic insight he created an army that defeated even Hannibal and asserted Rome's supremacy in Spain, Africa, and the Hellenistic East. He had a great appreciation of Greek (ancient Greek civilization) culture and enjoyed relaxing in the congenial atmosphere of the Greek cities of Sicily, conduct that provoked the anger of old-fashioned Romans such as Cato. Indeed, he was outstanding among those Roman nobles of the day who welcomed the civilizing influences of Greek culture that were beginning to permeate Roman society. His Greek sympathies led him to champion Rome's mission in the world as protector of Greek culture; he preferred to establish Roman protection rather than direct conquest and annexation. For 10 years (210–201) he commanded a devoted army at the people's wish. His position might seem almost kingly; he had been hailed as king by Spanish tribes, and he may have been the first Roman general to be acclaimed as imperator (emperor) by his troops; but, though convinced of his own powers, he offered no challenge to the dominance of the Roman nobility ensconced in the Senate except by normal political methods (in which he showed no outstanding ability). Reaction against his generous foreign policy and against his encouragement of Greek culture in Roman life led to his downfall amid personal and political rivalries, but his career had shown that Rome's destiny was to be a Mediterranean, not merely an Italian, power.

Scipio's influence outlived the Roman world. Great interest was shown in his life during the early Renaissance, and it helped the early humanists (humanism) to build a bridge between the classical world and Christendom. He became an idealized perfect hero who was seen to have served the ends of Providence. Petrarch glorified him in a Latin epic, the Africa, which secured his own coronation as poet laureate in 1341 on the Capitol, where, some 1,500 years earlier, the historical Scipio used to commune in the temple of Jupiter.