Best known for his work on TV's "Friday Night Lights," Chandler was also a member of the casts of current Best Picture Oscar nominees "Argo" and "Zero Dark Thirty."
"The Vatican" is described as "a provocative contemporary genre thriller about spirituality, power and politics -- set against the modern-day political machinations within the Catholic Church."
Chandler will portray Cardinal Thomas Duffy, the "charismatic yet enigmatic archbishop of New York, whose progressive leanings excite some and alarm others within the hierarchy of the Catholic Church," Showtime said.
Matthew Goode and Sebastian Koch will play supporting roles in the pilot, which is being directed by Ridley Scott and written by Paul Attanasio.
"Kyle Chandler is one of the most talented and sought-after actors working today and was a fantastic creative partner through five seasons of 'Friday Night Lights,'" David Nevins, president of entertainment at Showtime, said in a statement.
"With Kyle, Matthew Goode and Sebastian Koch, Ridley and Paul have put together a powerhouse cast to anchor this incredibly timely show."