Wilkerson married Gwendolyn Rose "Gwen" Carosso in 1953. He served as a pastor in small churches in Scottdale and Philipsburg in Pennsylvania, until he saw a photograph in "Life Magazine" in early 1958 of seven teenagers who were members of gangs in New York known as "Egyptian Kings" and the "Dragons" which had merged into a single gang called the "Egyptian Dragons". He later wrote that he felt the Holy Spirit move him with compassion and was drawn to go to New York, in order to preach to them. On his arrival, Wilkerson went to the court in which teenagers were being prosecuted. He entered the room and asked the judge for permission to tell them something, but the judge ejected him. Upon leaving, someone took a photo of Wilkerson, who then became known as the Bible preacher "who had interrupted the gang trial". Soon after this, he began a street ministry to young drug addicts and gang members, which he continued into the 1960s. He founded Teen Challenge in 1958, an evangelical Christian addiction recovery program in Brooklyn affiliated with the Assemblies of God, with a network of Christian social and evangelizing work centers.