John Krasinski (“The Office”) has been unlucky on the big screen until now. Neither “License to Wed” nor “Leatherheads” capitalized sufficiently on his natural charm, though George Clooney’s picture was surely an advance on Robin Williams’. Happily, “Away We Go” proves that the third time is the charm in more ways than one. Playing Burt, a laid-back, somewhat befuddled father-to-be on a spur-of-the-moment road trip with his pregnant girlfriend-wife Verona (Maya Rudolph, of “Saturday Night Live”), he comes across as winning and likable as he is on the small screen. And she’s no slouch, either.

Burt and Verona aren’t exactly your typical couple, living a rather shabby existence as they do in a run-down place in Colorado to be close to his parents Jerry (Jeff Daniels) and Gloria (Catherine O’Hara) when the child is born. But when the prospective grandparents prove themselves totally self-absorbed by announcing their intention to fulfill a lifelong dream and move to Belgium (selling their house in the process), the younger couple see no reason to stay put. Instead they embark on a continent-wide jaunt to visit friends and family, finding things to give them pause at every stop.

In Phoenix, there’s Verona’s friend Lily (Allison Janney), endlessly ranting against her husband Lowell (Jim Gaffigan) and their kids, who are as deeply unhappy as she is, though they suppress it more successfully. It’s clear that this family does not have happy days ahead.

Next is Tucson, where Verona’s sister Grace (Carmen Ejogo) is having some romantic doldrums, but nothing serious.

At the next stop, in Madison, Wisconsin, the true horror emerges. Burt’s old friend Ellen (Maggie Gyllenhaal), who now calls herself LN, is a brusque Women’s Studies professor whose hippie-like boyfriend (Josh Hamilton) and she practice a peculiar socio-domestic philosophy on their unfortunate son. Fleeing as quickly as possible, the couple wind up in Montreal, where Tom (Chris Messina) and Munch (Melanie Lynskey) appear on the surface to be living in perfect bliss with their brood of adopted children, until their private grief is revealed during a night on the town.

That’s supposed to be the end of the jaunt, but a phone call from Burt’s brother Courtney (Paul Schneider) necessitates a trip to Miami, where Courtney’s wife has suddenly left him and his young daughter. The episode leads to a bittersweet ending in which the traveling pair accept that neither marriage nor family is any guarantee of happiness, understanding that one must accept the natural ups and downs of life, however painful they might be.

One can interpret “Away We Go” as another chapter in director Sam Mendes’ cinematic dissection of American middle-class life, episodic in the way that “American Beauty” and “Revolutionary Road” were not, but equally critical. That’s not unfair, but here the execution is much looser—the look fashioned by production designer Jess Gonchor and art director Henry Dunn lacks the obsessive concern for visual perfection that was a hallmark of the earlier films—and the tone is finally less bleak, because while the black humor of the Phoenix and Madison sequences and the sorrowful tone of those in Montreal and Miami are sharply etched, they’re balanced by the genuine affection between Burt and Verona and the conviction that while they’ll inevitably make mistakes, they’ll be able to beat the odds.

That’s largely because of the winning turns by Krasinski and Rudolph, nicely set off against the more broadly-drawn supporting figures, who quite frankly flirt with caricature more suited to sketches than extended treatment. Of course, that’s what scripters Dave Eggers and Vendela Vida provide, and some of the cast manage better than others. Ejogo and Scheider, the most normal of the bunch, come off best, and Messina and Lynskey aren’t far behind. But the cluelessness of Daniels and O’Hara is cartoonish, and Janney’s vulgar motor-mouth act would be impossible to stomach if it went on much longer than it does. The Gyllenhaal episode is the most problematic, since it takes its target to such extravagantly outlandish lengths. But it too is short enough not to overstay its welcome.

Like most episodic road movies, “Away We Go” has a shapeless, meandering quality quite different from the precisely engineered structure of Mendes’ other films, a characteristic accentuated by Alexi Murdoch’s repetitive score. But the limberness of the leads and the affable nature of Mendes’ treatment soften the material’s harshness and make it go down easily. You should tag along with Burt and Verona on their journey of discovery.