By 1554, Whittingham made his way to Frankfurt, Germany, where he joined a group of Protestant exiles from Mary's reign. There, he met up with John Knox and became a supporter of Calvinism. He took over Knox's role as minister to the English congregation of exiles in Geneva. In Geneva, he started the work for which he is best remembered, a Bible translation that came to be known as the Geneva Bible.
In 1560, Whittingham returned to England, and was eventually made dean of Durham, an office he held at his death.