He was born in Molfetta. As a boy he apprenticed with a modest local painter Saverio Porta, (c1667–1725), escaping the religious career his parents had intended for him. By October 1724, he left Molfetta, and along with his contemporaries Francesco de Mura (1696–1784) and Giuseppe Bonito (1707–1789), he trained from 1719–23 in the prolific Neapolitan studio of Francesco Solimena, either with Solimena or his pupil, Nicola Maria Rossi.
Giaquinto followed a peripatetic career, with long sojourns in Naples, Rome (between 1723–53), Turin (1733 and 1735–39), and Madrid (1753–1761).
In 1723, he moved to Rome to work in the studio of Sebastiano Conca. He painted in San Lorenzo in Damaso, San Giovanni Calibita, and the ceiling at Santa Croce in Gerusalemme. In March 1727, with Giuseppe Rossi as an assistant, Giaquinto opened an independent studio near the Ponte Sisto, in the parish of Saint Giovanni of the Malva in Rome. In 1734, he married Caterina Silvestri Agate.
The first documented work by his hand is Christ crucified with the Madonna, Saint John Evangelist, and Magdalene commissioned in 1730 by king John V of Portugal for the cathedral of the Mafra.
In 1731, he received a prestigious commission, to execute frescoes in the church of San Nicola dei Lorenesi: Saint Nicholas water gush from cliff, three theologic and cardinal Virtues, and in the cupola Paradise. The latest restoration confirms Giaquinto's stylistic independence from Solimena, and reveals his stylistic dependence on Luca Giordano.
In 1738 Giaquinto returned to Rome, and during the next year he executed in fresco an Assumption of the Virgin for the church of Rocca di Papa, a commission for a relative of Pope Alexander VIII Ottoboni.
In 1740, Giaquinto became a member of the Academy of Saint Luke and donated his sketch of Immaculate Conception with Elias the prophet for the Turinese church of the Carmine, a canvas commissioned by marquis Giuseppe Turinetti di Priero, which finally reached Turin in 1741. A report of 1742 states that Pope Benedict XIV "was taken to the church of San Giovanni Calabita ... where he observed with much pleasure the restoration of that Church embellished with altarpieces from the Painter Signor Corrado Napolitano.
In Madrid, he was patronized by Ferdinand VI, and was ultimately appointed director of the Academy of San Fernando. His influence there was felt by painters such as González Velázquez, José del Castillo, and Mariano Salvador Maella.
His paintings include A Kneeling Male Nude. He returned to Naples in 1762 to decorate the sacristy in San Luigi di Palazzo, the royal monastery. He died in Naples in 1766.
He is described by some as an Italian François Boucher. Among his pupils in Molfetta was Niccoló Porta.