• Chris Pine as Edgin Darvis, a bard and former member of the Harpers.[9]
• Michelle Rodriguez as Holga Kilgore, a barbarian who was exiled from the Uthgardt Elk Tribe.[10][11]
• Regé-Jean Page as Xenk Yendar, a paladin who narrowly escaped the lich Szass Tam's "rise to power" in Thay and as a result, "ages more slowly than a normal human".[10][11]
• Justice Smith as Simon Aumar, a wild magic sorcerer who is the descendent of Elminster Aumar, a notable wizard.[10][12]
• Sophia Lillis as Doric, a tiefling druid[1] raised in the Neverwinter Wood by a wood elf enclave. She is a member of the Emerald Enclave and has organized a resistance against the Lord of Neverwinter who have targeted the forest "for its resources".[10]
• Hugh Grant as Forge Fitzwilliam, an ambitious rogue and con artist.[10]
• Daisy Head as Sofina, a Red Wizard of Thay[13][14] with a focus in necromancy and "ties to Thay's tyrannical magocracy".[10]
• Jason Wong as Dralas, a Red Wizard of Thay[15]
• Chloe Coleman[16]
• Rylan Jackson[17]

Additionally, cast members from the Dungeons & Dragons web series Critical Role will make cameo appearances in the film.[18] Comedy group Aunty Donna also provided voices for corpses in the film.[19]