The 39-year-old will appear as "The Color of Money" star, who appeared alongside Neal in 1963 classic "Hud", for which she won an Oscar and he was Oscar-nominated.
The movie, which is already in production and wraps soon, will see Keeley Hawes take on the role of the actress, with Hugh Bonneville starring as her husband, children's author Dahl.
"We are delighted that Sam has joined us, he is the perfect actor to play Paul Newman and a terrific addition to our already wonderful cast," the film's producer Donall McCusker told Deadline.
The casting announcement comes shortly after Heughan told U.S. late night host Jimmy Fallon on Monday, December 16 he hadn't been contacted by producers in relation to a potential James Bond role, despite swirling rumours.
"I can reveal right now that I am not James Bond," the actor said, before adding, "I'm waiting for the call." he said, before teasing, "Well, I haven't been told I'm not (James Bond)."