Writing for Allmusic, critic William Ruhlman wrote of the album "Prine took five years between his ninth studio album and this, his tenth—enough time to gather his strongest body of material in more than a decade... Prine's gifts for emotional revelation and off-the-wall humor are on display in abundance." Music critic Robert Christgau wrote "Occasionally too fantastic but never too bitter, the sagest and funniest of the new Dylans writes like he's resigned to an unconsummated life and sounds like he's enjoying one... I attribute its undeviating quality, gratifying variety, and amazing grace to talent, leisure time, and just enough all-star input. I wouldn't swear there's a stone classic here—just nothing I wouldn't be happy to hear again."
Alanna Nash of Entertainment Weekly gave the album an A+ rating, writing "John Prine's best work has always been slightly cinematic and hallucinogenic, full of images that transport as well as provoke. There's plenty of that on this new album The Missing Years... While little here is stunning — except for the Dylanesque Take a Look at My Heart, a dear sucker letter to Prine's ex-old lady's boyfriend, with a subdued cameo vocal by Bruce Springsteen — all the songs are keepers, perfectly relaxed and wry." Critic Lynn Van Matre of the Chicago Tribune wrote "One of the singer-songwriter's strongest and most wittily observant efforts, the album finds Prine at the top of his form in a mix of evocative folk-country ballads and more rocking fare... Goofily surreal and straightforwardly sentimental by turns, this one's a don't-miss for longtime Prine fans and anyone else with a taste for idiosyncratic singer-songwriters."