He specialized in small-scale pictures of subjects gleaned from the natural world such as floral still lifes and allegorical series showing animal kingdoms, the four elements, the senses, or the parts of the world. Obsessed with picturesque detail, van Kessel worked from nature and used illustrated scientific texts as sources for filling his pictures with objects represented with almost scientific accuracy.
Jan van Kessel painted many animals (especially insects) and flowers, as well as some mythological and biblical scenes. his choice of subject leaned towards those which included animals and plants. His pupils were his sons Jan van Kessel, junior and Ferdinand van Kessel.