A rich black woman, Mrs. Munson says that she donates monthly to Bob Jones University, citing it as a "good Bible college". Bob Jones University banned black students until the 1970s, and did not allow interracial dating until 2000.

Prior to filming, Tom Hanks had not seen The Ladykillers (1955), as he did not want it to prejudice the way he acted in the remake.

This is the first Coen brothers film where Joel Coen and Ethan Coen are both given directing and producing credits. They have shared these duties on all of their films, but Joel has always been listed as the director, and Ethan as producer. Although they both take turns performing the duties.

All the musical instruments were re-created by guitar maker Danny Ferrington, because, according to him, the owners of authentic antique instruments refused to lend them for the film. The strange "triple guitar" is a "harpolyre," but because it wasn't invented until the 1830s, it isn't historically correct for the Professor's spurious Renaissance band. The long-necked guitar-like instrument is a theorbo, played in late Renaissance and early Baroque music to accompany singing, provide color, and backup the Basso Continuo. Ferrington built it from scratch.

Several times at the beginning of the film, when Mrs. Munson is complaining about a neighbor's loud music, she repeats lyrics to the song to illustrate her displeasure. The song is "I Left My Wallet in El Segundo" (1990), by A Tribe Called Quest.

The exterior shot of the riverboat casino is an actual casino on the Mississippi River, in Vicksburg, Mississippi. The Ameristar lettering on the "paddlewheel" was edited out, and the movie casino's name put in its place. In the movie, the casino has closing hours while the Ameristar casino is a 24/7 operation (the entire parking lot beside the boat was emptied for the shot). Additionally, two large river bridges that would normally be at the left side of the frame, are edited out.

Before Professor Dorr (Tom Hanks) starts to go over the plans for the heist in the cellar, he sets playing as background music Boccherini's Minuet: this is the same piece which in the 1955 film version Professor Marcus (Alec Guinness) plays repeatedly on a gramophone record to convince his landlady that he and his fellow crooks are rehearsing as a string quintet.

The second Coen brothers movie filmed in Mississippi.

Marva Munson shows Professor G.H. Dorr her dead husband Othar's fife. This is an homage to Otha Turner (also known as Othar Turner), a famous fife and drum blues musician.

Plans to remake The Ladykillers (1955) date back to 1998 when Robert Harling was attached to direct.

Marva Munson (Irma Hall), the owner of the house the robbers use, bears the same name as the judge in the Coen Brothers' subsequent film, Intolerable Cruelty (2003). In both cases, the women are African-Americans.

The word "fuck" is used 89 times in the film.

The Professor's initial plan to trap and "immure" Mrs. Munson inside the tunnel is based on Edgar Allan Poe's Cask of Amontillado, in which Montresor, the main character traps another inside a wall in a cellar as an act of revenge. This idea is appropriate, as the Professor is an avid Poe enthusiast.

The name G.H. Dorr was taken from 19th century artist Gustave Doré.

Produced by Barry Sonnenfeld, who started out as the cinematographer of the Coen Brother's first three films.

Blake Clark, playing the football coach, was Coach Farmer Fred in The Waterboy (1998).

Bruce Campbell: at the dog food commercial shoot.

When Garth Panckake (J.K. Simmons) gets his finger severed, Gawian MacSam (Marlon Wayans) mentions the story of a man who got his penis cut off then had it reattached and even ended up filming a porn film. This is a reference to the real case of Lorena and John Wayne Bobbit, whose story hit the headlines in 1993 when she cut off her husband's penis and threw it out of her car window. Later it was found and surgically reattached, and John W. Bobbit did film two porn films (Uncut and Franckenpenis).