Sarpi was the son of Francesco Sarpi, an unsuccessful businessman, and Isabella Morelli, of a prominent but not noble Venetian family. His father died when Sarpi was a child, and he was brought up in poor circumstances by his pious mother and his maternal uncle Ambrogio, a priest. Delicate, studious, and clever, at 14 Sarpi joined the Servite order and at 20 became court theologian to the duke of Mantua, a post which gave him leisure to study Greek, Hebrew, mathematics, anatomy, and botany. Young Sarpi was known as La Sposa—“The Bride”—because of his modesty and moral seriousness. Of medium height, with a large brow, long nose, black eyes, and thin beard, he lived simply and suffered from poor health. He is reported to have possessed a photographic memory and to have been a most persistent scholar.

At 27 Sarpi was appointed provincial of his order and won a reputation as a firm but sensible ruler. He visited Rome several times and became friendly with Pope Sixtus V and the great theologian Robert Bellarmine. Continuing his anatomical studies, he discovered the valves of the veins that facilitate the circulation of the blood, and he was the first to demonstrate that the pupil of the eye dilates under the action of light. His many friends included Galileo, who thought no one in Europe could surpass Sarpi in mathematics, while Sarpi said of the astronomer's condemnation by Rome, “The day will come, I am almost sure, when men, better versed in these matters, will deplore the disgrace of Galileo and the injustice dealt so great a man.”

Venice, with its cosmopolitan population, had long followed a liberal religious policy, resisting any intrusion by Rome into its internal affairs. In 1606 Paul V demanded that Venice repeal a law restricting church building and hand over to him two priests, one charged with murder, whom the Venetian government intended to try before civil courts. When Venice refused, Paul excommunicated the Senate and the Doge (the Venetian head of state) and put the republic under an interdict, meaning that all priests were debarred from their functions.

Sarpi, having been appointed consultor to the government, wrote powerfully in support of the Venetian case. He argued that the pope was infallible only in matters of faith and that his interdict was invalid. Sarpi's basic tenet was that “princes have their authority from God, and are accountable to none but him for the government of their people.” It was in the public interest, he said, to fix limits on church building in a small city like Venice, for ecclesiastical property—already extensive—paid no taxes to the state. As for the two priests, while the church had every right to try them for crimes committed as priests, for crimes such as murder and adultery the state courts must be responsible. Sarpi concluded that Venetians were not bound to observe the interdict, and his advice was followed.

Sarpi wrote in a clear, witty style and argued not from legal textbooks but from the evident facts of history. He constantly argued, for example, that the pope's power should not exceed that of St. Peter. Sarpi's writings played an important part in sustaining Venetian morale and in winning sympathy abroad. Paul V had a powerful ally in Spain, then dominant in Italy, and when he threatened recourse to arms, Venice secured the support of France and even threatened to call on Protestant countries. Finally the Pope, fearing Venice would become Protestant, agreed to a settlement. The interdict was ended, and Venice handed over the two priests, reserving, however, its right to try churchmen before civil courts. “The Republic,” said Sarpi, “has given a shake to papal claims. For whoever heard till now of a papal interdict, published with all solemnity, ending in smoke?”

Sarpi refused to answer a summons to appear before the Roman Inquisition. On Oct. 5, 1607, he was attacked in the street and stabbed. He blamed the Roman Curia, but the charge has never been proved.

Between 1610 and 1618 Sarpi wrote the first full history of the Council of Trent (Trent, Council of) (1545–63), using Venetian archives and private papers, notably those of Arnauld du Ferrier, French ambassador to the council. Sarpi strongly criticized the council for not giving bishops more autonomy, for hardening differences with the Protestants, and for increasing the Curia's absolutism. The only one of Sarpi's writings to be printed in his lifetime, the History of the Council of Trent, appeared in London in 1619, under the pseudonym Pietro Soave Polano. Though put on Rome's Index of prohibited books, it went through several editions and five translations in 10 years.

The History, like most of Sarpi's writings, is a partisan work, written with one eye on the Protestants, whom Sarpi saw as Venice's potential allies against Rome and Spain. Similarly, in his extensive correspondence, Sarpi sought the friendship of all who took an independent line toward Rome, including French Huguenots and German Protestants, but there is no evidence to suggest that he himself was, in doctrine, anything but an orthodox Roman Catholic. Sarpi's quarrel was never with the Roman church but—as he saw it—with an interfering Roman Curia.

Sarpi became something of a hero to the Venetians and was sought out by foreign visitors. He continued to live frugally and, though excommunicated, he celebrated mass to the end. He died in 1623, and his last words—“Esto perpetua” (“May she endure”)—were, characteristically, a reference to Venice.