Lyrical themes explored on the album include religion, sex, cultural deviance, death, insanity, war, and homicide.

Despite receiving mixed reviews from critics, Diabolus in Musica peaked at number 31 on the Billboard 200, selling over 46,000 copies in its first week of sales.

Paul Bostaph returned to Slayer in early 1997 after his short-lived side project The Truth About Seafood, and the band entered the recording studio a few months later.

"[4] Adrien Begrand of PopMatters felt Slayer introduced characteristics to its music including tuned down guitars, murky chord structures, and churning beats.

[4] Araya held concern about the lyrics that King penned to "In the Name of God", voicing his opinion to guitarist Hanneman.

[26] Reviewing the 2003 Slayer box set Soundtrack to the Apocalypse, Adrien Begrand of PopMatters called Diabolus in Musica "a unique record [...] It's as if they're stepping in to show the young bands how to do it right, as songs like 'Bitter Peace', 'Death's Head', and the terrific 'Stain of Mind' blow away anything that young pretenders have put out.

"[5] Writing in The Guardian, journalist Joel McIver said although the album was as musically heavy and lyrically dark as any of Slayer's previous releases, it exhibited the groove-based style of the then-popular nu metal sound.

Reviewing a Slayer concert at Irving Plaza during the Diabolus in Musica tour, Ben Ratliff of The New York Times' panned the album for its murky production,[28] saying: "Eight of the 11 songs on Diabolus in Musica, a few of which were played at the show, are in the same gray key, and the band's rhythmic ideas have a wearying sameness too.

"[29] Reviewing Slayer's 2001 album God Hates Us All, Blabbermouth.net reviewer Borivoj Krgin described Diabolus in Musica as "a feeble attempt at incorporating updated elements into the group's sound, the presence of which elevated the band's efforts somewhat and offered hope that Slayer could refrain from endlessly rehashing their previous material for their future output.

"[30] Sarah Vowell of Spin gave the album a four out of ten rating, stating that "Fifteen years into Slayer's career, they're still deploying the same fast beats and sluggish riffs and batty banter."

"[23] Songs from the album were rarely played live following the return of drummer Dave Lombardo in 2002, with "Stain of Mind" being the only constant.