1704, "kernel of a nut;" 1708, "head of a comet;" from Latin nucleus "kernel," from nucula "little nut," diminutive of nux (genitive nucis) "nut," from PIE *kneu- "nut" (source also of Middle Irish cnu, Welsh cneuen, Middle Breton knoen "nut," Old Norse hnot, Old English hnutu "nut").
The general sense of "central mass or thing, about which others cluster or matter collects," is from 1762. In biology, "dense, typically rounded structure in a cell, bounded by membranes," from 1831. Later they were found to contain the genetic material. Modern meaning in physics, "positively charged central core of an atom," is from 1912, by Ernest Rutherford, though theoretical use for "central point of an atom" is from 1844, in Faraday.