JOHN PRINE needed to get into his comfort zone to finish a new album, so his wife reserved a room at the Omni Hotel in Nashville for a week. After nearly 50 years on the road, hotel rooms are a familiar enough sight. Following two bellmen to his suite, Prine settled in with four guitars and 10 boxes of legal pads to complete the album that would become The Tree of Forgiveness.

The highly-anticipated album, The Tree of Forgiveness, is Prine’s first collection of new material since 2005’s Grammy-winning Fair and Square. Rather than going out on a limb, Prine cultivated the themes that have brought international acclaim since the 1970s. For example, he can take a topic like loneliness and make it funny (“Knockin’ on Your Screen Door”) or heartbreaking (“Summers End”). Perfectly aligned with his quirkiest songs, “The Lonesome Friends of Science” makes its point through the characters he calls “those bastards in the white lab coats who experiment with mountain goats,” as well as the discredited planet Pluto and the towering Vulcan statue in Birmingham, Alabama.

Prine teamed with Grammy-winning producer Dave Cobb to record in Nashville’s historic Studio A, enlisting friends like Brandi Carlile, Jason Isbell, and Amanda Shires to sing along. The songs are new, although some had waited to be finished for decades, like a co-write with Phil Spector called “God Only Knows.” Another incomplete song, “I Have Met My Love Today,” now celebrates the unexpected spark that leads to lifelong romance — with a dash of youthful innocence. The musical arrangements may be simpler than on past efforts, yet his unique ability to distill complex emotions into everyday language remains fully intact.

Opening for Mr. Prine will be Valerie June.