According to Vitruvius (vii., preface) he lived during the age of Ptolemy Philadelphus, by whom he was crucified as the punishment of his criticisms on the king; but this account should probably be rejected as a fiction based on Zoilus' reputation. Vitruvius goes on to state that Zoilus also may have been stoned at Chios or thrown alive upon a funeral pyre at Smyrna. Either way Vitruvius felt it was just as well since he deserved to be dead for slandering an author who could not defend himself. Zoilus appears to have been at one time a follower of Isocrates, but subsequently a pupil of Polycrates, whom he heard at Athens, where he was a teacher of rhetoric.
Zoilus is especially notable for his role in the beginnings of Homeric scholarship. His monograph Homeric questions seems to have analyzed continuity errors in Homer, but also criticized the impropriety of Homer's depiction of gods indulging in allegedly inappropriate behavior. This monograph is widely regarded as the beginning of classical scholarship. Zoilus also wrote responses to works by Isocrates and Plato, who had attacked the style of Lysias of which he approved.
However, the Homeric questions led to his name becoming a byword for harsh and malignant criticism: in antiquity he gained the name Homeromastix, "scourge of Homer"; in the modern period, Cervantes calls Zoilus a "slanderer" in the preface to Don Quixote and there is also a (now disused) proverb, "Every poet has his Zoilus." Since his writings do not survive, it is impossible to know whether this caricature is justified.