Father and grandfather were also doctors. His father Johann Friedrich Hufeland was personal physician of the duchess Friederike of Saxony-Weissenfels. In 1765 he was appointed a personal physician of the duchess Anna-Amalia of Weimar. The family moved to Weimar when Christoph Wilhelm was 3 years old. 

Hufeland began his studies of medicine in Jena when he was 18, later he continued them in Göttingen. He took over the practice of his blinded father when he was 21. In Weimar he met Goethe, Schiller, Herder and Wieland and became their medical mentor. In 1786 a pox epidemic broke out there and Hufeland carried out a protection inoculation against it with success. He dealt among other things with the dangers of the apparent death. Because of his publications he became a member of the „kurfüstlich Mainzische Akademie zu Erfurt“ (electoral academy of sciences at Erfurt). In 1801 he became the personal physician for king Friedrich Wilhelm III in Berlin. Hufeland became dean of the medical department and professor of the University of Berlin. He treated destitute people freely in the polyclinic created by him. On the occasion of his 50 Years' Doctor Anniversary the city Langensalza gave him the honorary-citizen-right in 1833. Hufeland passed away in Berlin in 1836.