Castellio lahir pada tahun 1515 di [[Saint-Martin-du-Frêne]] di desa Bresse, [[Provinsi Dauphiné|Dauphiné]], sebuah desa yang berbatasan dengan [[Swiss]], Prancis, dan [[Savoy]]. Di bawah pemerintahan Wangsa Savoy, keluarganya menyebut diri mereka Chateillon, Chatillon, atau Chataillon. Setelah menempuh pendidikan pada usia dua puluh tahun di [[Universitas Lyon]], Castellio fasih berbahasa [[Prancis]] dan [[Italia]], serta menjadi ahli dalam [[bahasa Latin]], [[bahasa Ibrani]], dan [[bahasa Yunani]]. Selanjutnya, ia belajar [[bahasa Jerman]] saat ia mulai menulis karya-karya teologis dalam berbagai [[bahasa Eropa]].
HisPendidikan, educationsemangat, zealdan andpengetahuan theologicalteologisnya knowledgesangat wereluar sobiasa outstandingsehingga thatia hedianggap wassebagai consideredsalah tosatu beorang oneyang ofpaling theterpelajar mostpada learned men of his time &mdashmasanya; equalsetara, ifjika tidak notlebih superiortinggi, todari [[John Calvin]]. RegardingMengenai Castellio, according tomenurut ''A [[A Conscience Against Violence|ConscienceHati AgainstNurani ViolenceMenentang Kekerasan]]'' ofkarya [[Stefan Zweig]], [[Voltaire]] wrotemenulis: "WeKita candapat measuremengukur thekeganasan virulencetirani ofini thisdengan tyrannypenganiayaan byyang thedialami persecution to whicholeh Castellio waspada exposed atmasa Calvin's instance — althoughmeskipun Castellio wasmerupakan aseorang farsarjana greateryang [[scholar]]jauh lebih hebat thandari Calvin, whoseyang jealousykecemburuannya drovemembuatnya himkeluar out ofdari [[GenevaJenewa]]."<ref>{{cite book |title= The RightHak tountuk HeresyMenyesatkan: Castellio against Calvin |url= https://archive.org/details/righttoheresycas0000zwei |url-access= registration |last=Zweig |first= Stefan |year=1936 |publisher= The Viking Press |location= New York|page=[[https://archive.org/details/righttoheresycas0000zwei/page/89 89]] }}</ref>
Castellio later wrote that he was deeply affected and moved when he saw the [[death by burning|burning of heretics]] in [[Lyon]] by the French Inquisition,{{Sfn | Zweig | 1951 | p= 239}} and at the age of twenty-four he decided to subscribe to the teachings of the [[Protestant Reformation |Reformation]]. In the spring of 1540, after witnessing the killings of the early Protestant martyrs, he left Lyon and became a missionary for Protestantism.{{Sfn | Zweig | 1951 | p= 239}}
