Born at La Flèche in northwestern France, Picard succeeded Pierre Gassendi as professor of astronomy at the Collège de France in 1655. He helped to found the Paris Observatory and conducted fundamental researches into the size of the Earth. Using new instruments such as William Gascoigne's micrometer he established an accurate baseline and by a series of 17 triangles between Malvoisin and Amiens calculated one degree to be 69.1 miles (111.2 km). This result proved to be extremely valuable to Newton in his calculations on the attractive force of the Moon.

Picard also determined accurately the position of Tycho Brahe's observatory at Uraniborg (this information was necessary in order to analyze and interpret Tycho's observations). He further noted, but was not able to explain, an annual periodic motion of Polaris (approximately 40ʺ). James Bradley later explained this as the aberration of light.