Of noble birth, Altieri was in the service of the papal embassy in Poland from 1623 to 1627, when he returned to Italy to become bishop of Camerino. Until his appointment as cardinal by Pope Clement IX in 1669, he held numerous church offices, including papal ambassador to Naples. After a long conclave, the 79-year-old cardinal was elected pope on April 29.

Despite his advanced age, Clement held firm against French arrogance. Like his predecessor, he failed—largely because of King Louis XIV of France—to rouse Europe against the Turks, who were menacing the Mediterranean. He resisted Louis's demand that the collection of revenues from vacant sees were Louis's right. Clement organized papal finances and gave Poland considerable aid against Turkish invasion. He erected at Rome the Palazzo Altieri and the fountains in St. Peter's piazza. Well loved, he canonized the celebrated SS. Cajetan of Thiene (Cajetan of Thiene, Saint), Francis Borgia (Borgia, Saint Francis), and Rose of Lima (Rose of Lima, Saint), South America's first saint.