After graduation, Lucado become an associate minister at Central Church of Christ in Miami, Florida. His responsibilities initially included overseeing a singles' group and writing a column for the church's newsletter. After two years in Miami, the now newlywed Lucado and his wife, Denalyn, moved to Rio de Janeiro, Brazil to become full-time missionaries.
After serving as the senior minister at Oak Hills Church in San Antonio, TX for 20 years, Lucado announced in early 2007 that he was stepping down due to health concerns related to atrial fibrillation. Lucado has since resumed the more limited ministry role of writing and preaching at Oak Hills with co-pastor Randy Frazee, formerly of Willow Creek Community Church of South Barrington, Illinois. The Lucados have three daughters, Jenna, Andrea, and Sara.