According to Deadline, Isbell, 42, will make his acting debut as Bill Smith, an “adversary” to DiCaprio’s Ernest Burkhart.
While 'Queen & Slim' star Simpson, also 42, has been cast as “infamous rodeo champion and bootlegger Henry Grammer.”
'The Twilight Saga: Eclipse' actor William Belleau and 'The Irishman's Louis Cancelmi have also boarded the flick as Osage rancher Henry Roan and hustler Kelsie Morrison, respectively.
What's more, Jack Fisk has been added as a production designer.
The filmmaker's previous credits include 'There Will Be Blood', 'The New World', and 'The Revenant'.
The Apple Original movie is based on David Grann's best-selling book of the same name.
The Osage Nation were the richest people per capita in the world and were killed one by one after oil was discovered on their land. As the death toll increased, the newly-created FBI took up the case and unravelled one of the most monstrous crimes in American history.
Plemons plays the lead FBI agent Tom White in the investigation, which came to be known as the Reign of Terror.
And Lily Gladstone stars as Mollie Burkhart – an Osage married to Ernest (DiCaprio), the nephew of a powerful local rancher portrayed by De Niro.
Scorsese is directing and producing the movie for Apple with Eli Roth writing the screenplay. A release date is yet to be confirmed.
The Hollywood legend recently revealed that the coronavirus pandemic actually benefited 'Killers of the Flower Moon' despite the project being subject to numerous delays as a result.
He said: "I feel as we're playing with it now, it's had a layer in, along with the actual main characters, of that sense that everybody is on [the collusion].
"Even the kindly old shopkeepers and that sort of thing. They're in on it just by being there.
"In any event, it's given us time to read more, and do more with costumes, locations, the structure of the buildings, houses, types of rooms."
From Her To Eternity is the foundation stone that paved the way for Your Funeral...My Trial, Henry's Dream, Murder Ballads, Push The Sky Away,...
Noel Gallagher reckons no-one likes a do-gooder. He’s so wrong.
David Bowie fans across the globe have something very special to celebrate today as it has just been announced that the worlds's first David Bowie...
In a recent open letter to the Prime Minister, Boris Johnson, major players in the UK music industry, including Sir Mick Jagger, Sir Paul McCartney...
Megan Thee Stallion pulls no punches and is unapologetically outspoken on her latest single, 'Thot S**t'.
Hollis Lomax; consisting of Will Rowland (Keyboard/Vocals) Hugo Keays (Guitar) Will Ellis (Bass Guitar) and Rob Taylor (Drums), are excited about...
There is nothing more uplifting in this world than watching Billie Eilish - the face of moody teen angst - having so much fun in the video for her...