Growing up under a strict regime of his stepfather, he learned some fundamental contemporary astronomy from the book "Vorhof der Sternwissenschaft" by Christian Pescheck. Later he went to study at the "Mathematischer Salon" in Dresden.
He is said to have independently discovered Algol's variability in 1744 - more than a century after Montanari. On Christmas, 1758 (December 25-26, 1758) he made the first sighting of comet Halley on its first predicted return - predicted by Edmond Halley 1705 for 1758-59. While some speculate he discovered the comet with the naked eye, others (e.g., Admiral Smyth) say he used a reflecting telescope of 8 foot (2.4 meter) focal length.
In the following he was called to the court of the Elector of Saxony to teach the young principal, Friedrich August III. in astronomy. In recognition of this, the principal made him a member of the Leipzig "Ökonomische Sicietät" (Economical Society).
Besides astronomy, he studied agricultural botanics, and helped to introduce the potato as a common food in Saxony. He also used microscopes for biological studies, and introduced the lightning rod in Saxony.
After his death on February 21, 1788 he left behind a library of 3518 books, partly handwritten copies he had created from scientific works too expensive for him to purchase.
His former residence was detroyed during the Battle at Dresden in August 1813. In 1877, the city of Dresden has honored him with a monument close to his former residence. In 1935, the astronomical community honored him by naming a Moon Crater after him: Moon crater Palitzsch is situated at 28.0S, 64.5E and 41.0 km across. Near this crater there is a valley on the Moon, named Palitzsch Valley, from its proximity to the crater. Asteroid (11970) Palitsch, provisionally descignated 1994 TD, has been discovered on October 4, 1994 by P. Sicoli and P. Ghezzi.