He studied at Wittenberg, where he soon gained the friendship of Martin Luther. In 1519 he accompanied Luther to the great assembly of German divines at Leipzig, and acted as recording secretary. After teaching for some time in Wittenberg, he went to Frankfurt in 1525 to establish the Protestant reformed mode of worship. He had resided there only a month when he was called to Eisleben, where he remained till 1526 as teacher in the school of St Andrew, and preacher in the Nicolai church.
In 1536 he was recalled to teach in Wittenberg, and was welcomed by Luther. Almost immediately, however, a controversy, which had been begun ten years before and been temporarily silenced, broke out more violently than ever. Agricola was the first to teach the views which Luther was the first to stigmatize by the name Antinomian, maintaining that while non-Christians were still held to the Mosaic law, Christians were entirely free from it, being under the gospel alone.
In consequence of the bitter controversy with Luther that resulted, Agricola in 1540 left Wittenberg secretly for Berlin, where he published a letter addressed to the Elector of Saxony, which was generally interpreted as a recantation of his obnoxious views. Luther, however, seems not to have so accepted it, and Agricola remained at Berlin.
The elector Joachim II of Brandenburg, having taken him into his favour, appointed him court preacher and general superintendent. He held both offices until his death in 1566, and his career in Brandenburg was one of great activity and influence. Along with Julius von Pflug, bishop of Naumburg-Zeitz, and Michael Helding, titular bishop of Sidon, he prepared the Augsburg Interim of 1548. He endeavoured in vain to appease the Adiaphoristic controversy.
He died during an epidemic of plague on the 22nd of September 1566.
Agricola wrote a number of theological works which are now of little interest. He was the first to make a collection of German proverbs which he illustrated with a commentary. The most complete edition, which contains seven hundred and fifty proverbs, is that published at Wittenberg in 1592.