After definitively playing male lead Don Draper in the landmark cable TV series “Mad Men” from 2007 to 2015, the charismatic Jon Hamm lost his way.

He played himself in episodes of both “Barry” and “Curb Your Enthusiasm.” But his other work did not stick. For a time, he was best known as the pitchman voice of Mercedes Benz (“the best or nothing”).

Who would have guessed that the best post-Draper role Hamm would play would be Gregory Mcdonald’s popular, wise-cracking sleuth Irwin Maurice Fletcher, better known as Fletch, previously played on the screen by Chevy Chase?

“Confess, Fletch” is the second in the series of novels by Mcdonald. The film begins with Fletch arriving from Rome — where he enjoyed a whirlwind romance with an Italian heiress named Angela (charming Chilean actor of Italian descent Lorenza Izzo) — at a triple-decker in Boston’s South End (the film was shot in Boston) and finding a dead body.

The plot, which is complicated, involves nine stolen masterpieces, including a Picasso (Boston? Stolen paintings? Really?). Angela, whose rich father was supposedly kidnapped, believes that the paintings were stolen by her former stepmother, the Countess de Grassi (a delightful turn by Academy award winner Marcia Gay Harden), and sent to a germophobic art dealer in the Back Bay named Horan (an amusing Kyle MacLachlan).

The film reunites Hamm with John Slattery, his partner in crime on “Mad Men.” Slattery plays former investigative reporter Fletch’s foul-mouthed former editor, who now works for a Boston newspaper known as the Sentinel.

The Boston police arrive in the form of Detective Morris Monroe (Roy Wood Jr.) of Dorchester, nicknamed “Slow” because he gets his man or woman, but he takes his time. Fletch is the obvious murder suspect. Monroe’s sidekick is newbie Griz (a likably offbeat Ayden Mayeri). She takes an intense dislike to Fletch, who combines keen intelligence with a wide streak of sarcasm. Fletch’s sign-off when he hops out of an Uber is “five stars.”

Harden, who is not Italian, manages to pull it off, matching Fletch gimlet for gimlet, expecting, if not demanding, to be seduced by him and addressing him hilariously as “Flesh.” The Countess claims to be “half Italian, half Brazilian and half French.”

Director Greg Mottola (“Superbad”) has assembled a first-rate cast. Annie Mumolo is a scream as a drug-addled South End resident with a small dog that takes large leaks in her home (I think I used to live upstairs from this person).

The Warren Tavern and the Copley Plaza get a shout out. Fletch goes to Chinatown and asks a young resident where he can get fireworks. “New Hampshire,” he is told. The fireworks bit in the screenplay adapted by Zev Borow (TV’s “Lethal Weapon”) and Mottola is both very dangerous-looking and not particularly credible. The writers try to update Mcdonald’s 1976 book with references to influencers and “harmonious disunitings.”

Former Los Angeles Times reporter Fletch dares to wear a Lakers cap in Boston.

Hamm and Wood make a fine couple of mismatched buddies, and it would be fun to see them bust more cases. But Hamm in particular triumphs in this role. He doesn’t make us forget how much fun Chase was. But Hamm puts his own stamp on it, and he plays it with the effortlessness he had in “Mad Men.”

“Confess, Fletch” is not “the best or nothing.” But in large part thanks to Hamm, it is adroitly played and very entertaining.