He was active in reforming the church in Nuremberg, which drew unfavorable attention from religious conservatives.
Spengler was one of Luther's supporters mentioned by name in Pope Leo X's bull Exsurge Domine, issued on 15 June 1520, threatening to excommunicate Luther and his followers if they did not submit to the pope.
Spengler and the Nuremberg town council continued to reform the church in Nuremberg throughout the 1520s, and in 1525, Spengler traveled to Wittenberg to consult Luther and Philipp Melanchthon about the possibility of converting the Benedictine Ägidienstift into a Protestant gymnasium.
In 1528, Spengler worked with the other reformers to convince the Elector of Saxony, John the Steadfast to authorize a canonical visitation, an activity that had previously been conducted exclusively by Roman Catholic bishops.
Spengler participated in the negotiations at the Diet of Augsburg in 1530, where he was a vocal defender of strict Lutheranism.