In “Mississippi Grind,” two gamblers — one a handsome, upbeat younger man, the other an older guy who hasn’t played life well — team up for a trip down the Mississippi River to New Orleans.

Ryan Reynolds (“Woman in Gold,” “The Proposal”) and Ben Mendelsohn (“Bloodline,” the New Orleans-shot “Killing Me Softly”) play Curtis and Gerry. After meeting at a poker game in Dubuque, Iowa, they gamble their way through such river locales as St. Louis, Memphis and Tunica. All the while, their sights are set on a high-stakes poker game in the Crescent City.

Anna Boden and Ryan Fleck wrote and directed “Mississippi Grind,” which opens Friday at the Prytania Theatre. A team since 2002, their previous collaborations include “It’s Kind of a Funny Story,” “Sugar” and “Half Nelson.”

Boden and Fleck got the idea for “Mississippi Grind” while they were shooting “Sugar,” a film about a Dominican immigrate who plays minor league baseball. Filming in Iowa, the New York-based filmmakers encountered Mississippi River casinos for the first time during “Sugar” production.

“We love learning about places we ordinarily wouldn’t go to and people we wouldn’t normally meet,” Fleck said last week in New Orleans, the river city where they shot most of “Mississippi Grind.”

The Iowa casinos that introduced Fleck and Boden to riverboat gambling were the opposite of glamorous, Fleck said.

“Sort of anti-Las Vegas,” he said. “We thought they were really interesting locations. And later we kept throwing those locations around, thinking, ‘What if two guys meet in one of these poker rooms and then go down river for some big score?’ It’s an old-school setup, but we take it in unconventional directions.”

Reynolds’ Curtis and Mendelsohn’s Gerry, in addition to gambling on riverboats, visit dog tracks, horse tracks, off-track betting parlors and numerous dive bars. Boden and Fleck did their homework for the film by doing the same.

“We met people in these off-the-beaten path places,” Fleck said. “We talked to poker players, heard their stories. A lot of that found its way into the film.”

In “Mississippi Grind,” the impetus for the journey Curtis and Gerry take is the older man’s fantasy that his new friend is a lucky charm.

“Gerry has an addiction to losing,” Fleck said. “But he’s got a plan that he thinks will make him a winner. Gerry is always looking for someone to save him. It happens to be Curtis at the moment.”

Fleck and Boden were delighted to bring leading men Reynolds and Mendelsohn aboard “Mississippi Grind.” They had a hunch that Mendelsohn and Reynolds would make a good team.

“But we didn’t think they’d hit it off as well as they did,” Fleck said. “I hope that shows on the screen. Even when Ben Mendelsohn is doing absolutely nothing, he’s one of the most interesting people. That’s the quality he had when we met him. And it’s not like he just sits there, moping around. He’s a charming, funny person who really lights up the room.”

The filmmakers took care to show the places Gerry and Curtis travel to on their way to New Orleans. Each stop gets a montage of its local landmarks accompanied by blues music.

“Because it’s a road movie, we wanted to feel the shifting landscapes and get a sense of the cities and the towns along the way,” Fleck said.

“Mississippi Grind” production spent four months in New Orleans. The film also shot in Mississippi, Alabama, Baton Rouge and, briefly, Iowa. “I’m happy that the final third of the movie actually shot New Orleans for New Orleans,” Fleck said. “Because it’s such a beautiful city, I didn’t want to fake that.”