In this reality-based biopic of the late Portland cartoonist John Callahan, Gus Van Sant combines the inspiring quality of his conventional crowd-pleasers “Good Will Hunting” and “Finding Forrester” with the looser, more irreverent approach of his smaller independent projects. “Don’t Worry, He Won’t Get Far on Foot”—a title taken from one of the wheelchair-bound artist’s best-known panels—is a canny blend of the director’s different sides, an incisive portrait of a troubled eccentric that manages to be both broadly uplifting and quirkily entertaining.

The film is anchored not only by Van Sant’s sensitive, generous, time-shuffling screenplay and imaginative direction (which dovetails with editing, by him and David Marks, that genially employs devices like split screens and deliberately old-fashioned swipes) but by a virtuoso lead turn from Joaquin Phoenix, who holds nothing back in portraying Callahan. A goodly portion of the film is devoted to his early life as a free-wheeling young alcoholic (he admits having started drinking at 13) whose pessimistic outlook originated in his abandonment by a mother he never knew but longed to find (and, in this version, hallucinated about—she’s played by Mireille Enos) and life as an adopted child who never quite felt comfortable with the family who took him in.

The turning point comes during a raucous night out, when he bumps into wild man Dexter (Jack Black) at a party. The two drink the evening away, and while driving to yet another bash with Dexter at the wheel, they get into an accident that leaves John a quadriplegic. His hospitalization and physical therapy are depicted in boldly realistic strokes, though the appearance of as angelic a nurse as Annu (Rooney Mara) is a turn that most recovering patients would rarely experience.

After a grueling stay in traction and rehab, Callahan is speeding around the city recklessly in his motorized chair, still as given to drink as he ever was. He’s hired a fellow to help him at home, but the place is still a mess, and when left to fend for himself, his need for booze sometimes leads to domestic catastrophe, given his physical limitations. Support comes in a chance meeting with Annu, now a flight attendant, and in his discovery that some people are taken with his edgy drawings and their equally edgy captions; the cartoons will earn him recognition and admiration, as shown in a well-attended public presentation to an appreciative audience, including Annu.

But what ultimately ties the film together and gives it a real arc, even in the face of the chronologically scattershot structure, is Callahan’s desperate decision to join an AA group led by New Agey sponsor Donnie, a rich guy played by Jonah Hill, almost unrecognizable with blonde hair and beard, with grace, charm, and no little poignancy toward the close. The members of Donnie’s posse are a no-nonsense crew (one of them is Udo Kier, getting off some cheeky lines, as also do Kim Gordon and Beth Ditto), forcing John to a degree of honest introspection that culminates in his completing the AA steps of recovery, including apologies all around, including a reunion with Dexter.

“Don’t worry” ends on an upbeat note, but it’s by no means a simply “be happy” denouement, and it’s more a sweet-and-sour movie than one swimming in sugar. Van Sant manages both to get you rooting for Callahan even as you recognize the sadness of his self-destructiveness. Phoenix is an important part of the mixture, catching the divergent aspects of the cartoonist’s personality with both flamboyance and precision. He eagerly seizes on the different opportunities the screenplay provides—from a giddy sequence in which a bunch of good-natured skateboarding kids help Callahan after he takes a fall on the street (and enjoy seeing his oddball drawings) to a starchy one in which he’s accosted by an old lady who hates his cartoons.

Hill, meanwhile, supports Phoenix with a turn that’s deceptive: while it seems as though he’s merely gliding along, he’s actually filling the role with perceptive, and surprisingly wide-ranging, emotional undercurrents. And though Mara might not be able to make the resplendent Annu a completely convincing character, it’s unlikely that any actress could have; there’s just a fairy-tale quality to the subplot that strains credulity.

As shot by Christopher Blauvelt, the picture has a straightforward look that doesn’t glamorize the locations, and the images are enhanced by Danny Elfman’s hip but warmhearted score.

You might want to see “Don’t Worry, He Won’t Get Far on Foot” at a theatre near a good bookstore, because after the credits roll you could immediately want to go and buy a volume of Callahan’s cartoons.