In 1841, Ryle was ordained as a minister in the Church of England. In his first position in a rural parish he developed the plain and direct style of communication that would mark his future ministry. He served at several churches for the next forty years, during which time he wrote hundreds of evangelistic tracts. He was a wildly popular writer. His tracts sold more than 12 million copies in his lifetime, and were eventually translated into about a dozen European and Asian languages.

While his ministry flourished, Ryle’s home life was challenging. In 1844, he married his first wife, who died in 1847. He married again in 1849. The couple was happy, but his wife’s health was poor, so the pastor seldom travelled and practically raised his children alone. When his second wife died in 1860, he became a single father with five children between 2 and 14 years old.

Despite these hardships, Ryle became a leader among the evangelical clergy in his day. In 1880, he was appointed the first bishop of the newly formed diocese of Liverpool. Because the diocese was new, it had no system of leadership, no formal administration. During his tenure as Bishop of Liverpool, Ryle raised enough funds to build 90 new houses of worship, ordained over 500 deacons, 500 priests, and at least 45 salaried lay Scripture readers and 31 Bible women. He founded the Lay Helpers Association, an organization that oversaw Sunday schools, Bible classes, mission services, and cared for sick.