Antonio Pasqualin Lotti was born in Venice on January 5, 1667. His father Mattio Lotti was employed as an organist in Hanover from 1666 to 1679. In 1683, at the age of 16, Antonio studied with Giovanni Legrenzi (1626 - 1690). In 1687 he began to sing at the Cappella Ducale di San Marco. This year he was also one of the first to join the "Sovvegno dei musicisti di Santa Cecilia", a form of supportive musicians' association.

At the beginning he was an old cantor, later he became second organist in the chapel of San Marco. In 1693 his first opera "Il trionfo dell'innocenza" was performed at the Teatro San Angelo. Twenty of his operas have been performed in Venice over the course of twenty-four years. At that time, his opera had caught the attention of the Crown Prince Friedrich August (1696 - 1763) of Saxony. From 1697 to 1707 Lotti was also chapel master of the “Scuola dello Spirito Santo”. In 1704 he was elected the first organist in the Basilica of San Marco. In 1705 Lotti had a collection of madrigals published in Venice: "Duetti, terzetti e madrigali a piu voci". In 1714 he married the soprano Santa Stella (approx. 1686 - 1759) from Bologna.

Following an offer of employment by the Saxon Crown Prince Friedrich August II, Lotti was given leave of absence by the procurators of St. Mark's Basilica on July 17, 1717 and traveled to Dresden on September 5, 1717 with his wife and son, along with a group of Italian musicians, including the Castrat Senesino (1686 - 1758), the bass player Giuseppe Boschi and the soprano Margherita Durastanti. The librettist Antonio Maria Lucchini also accompanied her. Much of Lotti's concert sacred music, written in Venice, has survived due to his time in Dresden. His student Jan Dismas Zelenka was particularly important for the preservation of Lottis music. These are individual "Kyries, Glorias and Credos" and "Psalms for Vespers". His “Credo in F” with the famous “Crucifixus” movement belonged to these works. Lotti composed three operas in Dresden, "Giove in Argo", "Ascanio" and "Teofane" and "Il quattro elementi", a musical entertainment.

Lotti returned to Venice in October 1719, where he focused on writing sacred music and returned to his position at San Marco. It is not known whether he deliberately decided not to compose operas anymore or whether this was due to the circumstances. Lotti was finally elected "Maestro di cappella" on April 2, 1736. Just over a month after taking office, he composed the madrigal "Spirto di Dio ch'essend'il mondo" for the annual "Marriage to the Sea" (Sposalizio del Mare) Lotti also taught and composed at the "Ospedale dei Mendicanti" and the "Ospedale" degli Incurabili ”, two of the four Ospedali Grande in Venice that were run by the state as schools for orphans and forsaken children - usually children of courtesans. The schools were financed by wealthy benefactors who also sent their daughters to the Ospedali for their musical education. Lotti's contemporary Antonio Vivaldi (1678 - 1741) performed similar services at the "Ospedale della Pietà".

Lotti died on January 5, 1740 of dropsy (edema). He was buried in the church of S. Geminiano at the western end of Piazza S. Marco, which was demolished by Napoleon in 1807. Lotti's music is characterized by the use of suspensions, chromatics, discords and modulations. He is also a passionate exponent of word painting, with words like descendit and ascendit that are often sung in descending or ascending scales. He writes with great care for voices and technically highly complex cannons and fugues. His music had a huge impact on his contemporaries. Manuscripts of Lotti's music have survived from Handel's estate, and Handel's choral work identified a growing catalog of "bonds" at Lotti. The libretto of Handel's opera "Ottone" is based on Lotti's "Teofane". Handel's "Giove in Argo" also uses the same libretto as Lotti, with only a few modifications. JS Bach's own library contained a copy of Lotti's “Missa Sapientiae” and it is believed that this influenced him in the composition of his Mass in B minor. Lotti met both Handel and Bach. Of the twenty-four operas that Lotti wrote, only seven have survived: Alessandro Severo, Ascanio, Costantino, Foca superbo, Giove in Argo, Polidoro and Teofane. Arias and extracts from nine others have also been preserved, seven are considered to be completely lost. Although many arias are preserved in collections, they still have to be associated with a specific opera. Only two of his eight oratorios are said to have survived: "Il voto crudele" and "L'umiltà coronata in Esther".