Oprah Winfrey in The Color Purple but what is Tom Arnold if he isn’t primarily an actor? I’m looking at his IMDB page and if someone with that many acting credits isn’t considered an actor then I’m not sure I understand the question.
Harold Russell in The Best Years of Our Lives. This movie came up in the thread about decades. Harold Russell had never acted before, he played an Army veteran who had lost his hands, exactly what he was. From this role he became the only actor to win two Oscars for the same role, one for Best Supporting Actor and another special Oscar for being an inspiration to returning WWII veterans.
Bosworth is a good choice, his first role, and even though the movie kind of sucked his performance wasn’t bad.
Andre the Giant in The Princess Bride. You could argue that it didn’t really require much acting, or that he’d been “acting” his way through his wrestling career, but this really was unlike anything he’d done before, and he really did do a good job (If he’d done a bad job, you’d have known it). He was immensely proud of his role, showing it off when he could. I just recently read Cary Elwes’ book As You Wish… about the making of the film, and Andre comes of as a sympathetic, gentle, and doomed creature (“We don’t get much time, us small and big guys,” he said, referring to the often short lives of the very large and the very big, plagued as they are with health problems.)
She’s famous as an actor-turned-politician, but Helen Gahagan (later known as Helen Gahan Douglas) only had one movie role – as Ayesha* in the definitive 1935 version of H. Rider Haggard’s She[, where she played the evil powerful queen, the original “She-Who-Must-Be-Obeyed”. Her appearance and style undoubtedly influenced the Evil Queen in Disney’s Snow White and the Seven Drawfs two years later, and other Evil Queens years later.
*actually, for some reason they changed her name in the movie to “Hash-a-Motep,” but She’s “Ayesha” in Haggard and all other adaptations.
Dwight Yoakam made a great drunken, violent (stereotypical) redneck in Slinglblade.
ISTR being touched by Sean Combs’s (or whatever iteration of his name he was using at the time)performance in *Monster’s Ball.*It was really just a bit part, though it’s his story that is the catalyst for everything that follows. I don’t know, it really stuck with me long after the film ended.
I’m not sure how the OP is defining “one-off” performances, but all of those people had acting roles before and after their breakout performance (as did Tom Arnold, and Oprah had many roles after her first one).
If we are talking about non-actors who had a star performance, you have to include drill instructor F. Lee Ermey in Full Metal Jacket, which led to a considerable film career.