In 1735, Guardi moved to the workshop of Michele Marieschi, where he remained until 1743. His first certain works are from 1738, for a parish at Vigo dAnuania, in Trentino. In this period he worked alongside his older brother, Gian Antonio. The first work signed by Francesco is a Saint Adoring the Eucarist (circa 1739).
His works in this period included both landscapes and figure compositions. His early vedutas show influence both from Canaletto and Luca Carlevarijs. On February 15, 1757, he married Maria Mattea Pagani, the daughter of painter Matteo Pagani. In 1760 his brother Gian Antonio died and his first son, Vincenzo, was born. His second son, Giacomo, was born in 1764.