Smith graduated from LIFE Bible College and was ordained as a pastor for the International Church of the Foursquare Gospel. In the late '50s Smith was the campaign manager and worship director for healing evangelist Paul Cain. After being a pastor for a different denomination, he left his denomination to pastor a non-denominational church plant in Corona, California and eventually moved to a church called Calvary Chapel in Costa Mesa, California in December 1965. It was the only church on Church Street in Costa Mesa. The church had been planted by Pastor Floyd Nelson as a ministry to shut-in's begun with a small group of people in a mobile home park populated mainly by senior citizens in 1962. From there they moved to a Girl Scout building and eventually to Church Street which is where the church was meeting when Chuck Smith was hired as the "pulpit pastor."

In March 1968, Smith brought into his home pentecostal evangelist Lonnie Frisbee with his wife Connie. Lonnie was 18 years old. Chuck Smith paired him up with John Higgins who already had a Bible study going for youth and they started a Christian commune called "The House of Miracles." John and Lonnie went out into community to reach the youth with the gospel during the early days of the Jesus movement.

The church in Santa Ana grew, and as of 2006, 35,000 people attend. Over 1,000 churches have branched out from his church. Some of these churches are led by those whom Smith discipled including: Greg Laurie, Jon Courson, Mike MacIntosh, Joe Focht, Raul Ries, Xavier Ries, Skip Heitzig, Bil Gallatin and Malcolm Wild.

At its beginning, Calvary Chapel operated as a cross-cultural missions organization that bridged the "generation gap" as it existed during the Vietnam War period. Calvary Chapel was a hub of the "Jesus People" phenomenon that existed at that time and was featured in Time Magazine for its success among "hippies" and young people. Calvary Chapel pioneered a less formal and contemporary approach in its worship and public meetings. For example, it did outreaches on the beach and baptisms in the Pacific Ocean. Much of Contemporary Christian Music (CCM) has it roots in Calvary Chapel worship music. Calvary Chapel's rolling commentary style of preaching kept the Calvary Chapels close to the text of the Bible and was readily understandable by many hearers. Calvary Chapel early developed its own internal training for multiplication of church leaders and pastors. By pioneering a more informal and contemporary style in its church practices, Calvary Chapel reached large numbers in Costa Mesa, CA and expanded easily by adding many pastors and new congregations in many locations. The impact of Chuck Smith and Calvary Chapel on evangelical Christianity is profound and widespread and largely unheralded. Rather than being a teacher of systems and how to grow a large church (all the things that frustrated him in his denominational experience), Chuck Smith teaches the Bible at pastors conferences modeling in word and deed what he feels is the critical core of Calvary Chapels.

There are some who criticize Calvary Chapel churches for a perceived dogmatic approach and losing their connection to their founding principles of the 1960s. Those defending Calvary Chapel would say that Calvary Chapel has not changed, but as culture has become more egalitarian, it is more averse to this type of approach.

Chuck Smith is the author and co-author of several books. Titles of his books include Answers for Today; Calvary Chapel Distinctives; Calvinism, Arminianism & The Word of God; Charisma vs. Charismania; Comfort for Those Who Mourn; Effective Prayer Life; Harvest; Living Water; The Claims of Christ; The Gospel According to Grace; The Philosophy of Ministry of Calvary Chapel; Why Grace Changes Everything; Love: The More Excellent Way; The Final Act; and others.