He was a friend and perhaps pupil of Blas de Prado, an artist famous for his still lifes whose mannerist style with touches of realism the disciple developed further.
For approximately twenty years, patronized by the city's aristocracy, he pursued a successful career as an artist in Toledo painting religious scenes, portraits and still lifes.
On August 10, 1603, Sánchez Cotán, then in his forties, closed up his workshop at Toledo to renounce the world and enter the Carthusian monastery Santa Maria de El Paular.
His concern with the relationships among objects and with achieving the illusion of reality through the use of light and shadow was a major influence on the work of later Spanish painters such as Juan van der Hamen, Felipe Ramírez, the brothers Vincenzo and Bartolomeo Carducci and, notably, Francisco de Zurbarán.
Although his religious paintings have a primitive sensitivity and a peaceful rhythm, Cotán's high stature in art history rests exclusively on his still lifes, of which only a few are extant.
Sánchez Cotán established the prototype of the Spanish still life depicting pantry items, called a bodegón, composed mainly of vegetables.
Each form is scrutinized with such intensity that the pictures take on a mystical quality, and the reality of things is intensified to a degree that no other seventeenth-century painter would surpass.