Designed by Ira Louvin, the cover features the brothers standing in a rock quarry, dressed in matching spotless white suits and black ties, in front of a 12-foot-tall (3.7 m) plywood rendition of the Devil, as several hidden tires soaked in kerosene burn behind them as fire and brimstone.

Mark Deming stated in his AllMusic review: "You don't need to share the Louvin Brothers' spiritual beliefs to be moved by the grace, beauty and lack of pretension of this music; Satan Is Real is music crafted by true believers sharing their faith, and its power goes beyond Christian doctrine into something at once deeply personal and truly universal, and the result is the Louvin Brothers' masterpiece.

"[2] Don Yates of No Depression called the album a "bold statement of its title signified the uncompromising nature of the Louvins’ beliefs.

"[5] Critic Scott Walden compared the Louvins' music to the Velvet Underground; "Their comprehension of the tortured throes of a drunkard's Satan-infested soul are no less profound than Lou Reed's own understanding of a heroin junkie wrestling with a world devoid of meaning beyond the piercing tip of the needle...

There is a reason why songs from this album have been performed by the more commonly accepted genius of artists such as Gram Parsons, Johnny Cash, and Emmylou Harris.

In 2024, Gravity Falls creator Alex Hirsch parodied the cover and title with a fictional song called Cipher Is Real for The Book of Bill.