- Tommy Lee Jones as Ed Tom Bell
- Javier Bardem as Anton Chigurh
- Josh Brolin as Llewelyn Moss
- Woody Harrelson as Carson Wells
- Kelly Macdonald as Carla Jean Moss
- Garret Dillahunt as Wendell
- Tess Harper as Loretta Bell
- Barry Corbin as Ellis
- Stephen Root as Man who hires Wells
- Rodger Boyce as El Paso Sheriff
- Beth Grant as Carla Jean's mother
- Ana Reeder as Poolside Woman
- Matt Geistler as Poolside Man
- Josh Blaylock and Caleb Jones as Boys on Bikes
- Gene Jones as Gas Station Proprietor
- Kathy Lamkin as Desert Aire Manager
The role of Llewelyn Moss was originally offered to Heath Ledger, but he turned it down to spend time with his newborn daughter Matilda.[22] Garret Dillahunt was also in the running for the role of Llewelyn Moss, auditioning five times for the role,[22] but instead was offered the part of Wendell, Ed Tom Bell's deputy. Josh Brolin, who was not the Coens' first choice, enlisted the help of Quentin Tarantino and Robert Rodriguez to make an audition reel. His agent eventually secured a meeting with the Coens and he was given the part.[22]
Javier Bardem nearly withdrew from the role of Anton Chigurh due to issues with scheduling. English actor Mark Strong was put on standby to take over, but the scheduling issues were resolved and Bardem took on the role.[22]