In 1818, Despretz started working as répétiteur in chemistry at Polytechnique, in Paris, under Joseph Louis Gay-Lussac (1778-1850) who mentored his early research.
In 1824, he was appointed to teach at the prestigious Lycée Henri-IV, first as adjunct professor, then as holder of the chair of physics.
In 1831, César Despretz was briefly appointed to the chair of physics at Polytechnique to replace Claude Pouillet (1791-1868) who had resigned for health reasons after only a few months in office.
In 1841, Despretz succeeded Félix Savart (1791-1841) in the physics section of the French Academy of Sciences.
César Despretz became a foreign member of the Royal Society in 1862, a few months before his death at the age of 71.