Soto resigned from this post suddenly and headed for the abbey of Montserrat, hoping to join the Benedictines, but he was instead led to the Dominicans, entering their community at San Pablo de Burgos in 1524 and becoming professor of dialectics at their Segovia house of studies in 1525.

Steering the council away from compromise with the Protestants, he served as one of the principal defenders of tradition on such key questions as original sin, predestination, justification, the scriptural canon, and the authority of the Vulgate Bible.

That same year he took part in the celebrated debate held at Valladolid on the treatment of New World natives, joining his Dominican brethren in a thorough condemnation of the idea that the Indians were inferior beings worthy of enslavement.

In addition to producing such influential philosophical and theological works as the Summulae (1529), a manual of logic; De natura et gratia (1547), a polemic against Protestant soteriology; and his commentaries on Aristotle (1543 and 1545), on Paul's epistle to the Romans (1550), and on Peter Lombard's Sentences (1557), Soto contributed significantly to the development of political and legal theory, principally through his De iustitia et iure (1553), his most important jurisprudential work, in which he proposed that the ordinance of reason (rationis ordinatio) was the mechanism by which laws could be evaluated.

Like his fellow Spanish Dominicans Vitoria and Cano, Soto contributed substantially to the reinvigoration of Roman Catholicism in the sixteenth century by strengthening and broadening the theological curriculum, by stressing the need for continuity with the scholastic tradition (especially with Thomism), and by actively seeking social justice.

This opus was also considered as one of the first attempt of systematisation of Contract Law,[13] even if this characteristic must be reevaluated in light of previous works of german legal thinkers like Matthew of Kraków and Konrad Summenhart [de].

[14] More conservative than the later members of the School of Salamanca,[15] Soto believed that, although contractual freedom stemed from natural law does indeed exists,[16] it must been more supervised by the authorities, which are attentive to public interests.

[23] For him, the rich and the poor are bound in a symbiotic relation of mutual necessity, inasmuch as the second need the material support of the first to survive but the first need also the second to apply charity and get the salvation of their souls.