The statement that describes the major difference between prokaryotic and eukaryotic cells is:
Eukaryotic cells have a membrane-bound nucleus; prokaryotic cells do not.
This is a fundamental distinction between the two types of cells, as prokaryotic cells (like bacteria) lack a true nucleus and other membrane-bound organelles, while eukaryotic cells (like those in plants, animals, fungi, and protists) have a defined nucleus and organelles.