-Grant Gustin - "Barry Allen / The Flash" - a Central City assistant police forensic investigator who receives his powers after being caught in a chemical explosion at a lab caused by a lightning strike following an incident at the S.T.A.R. Labs particle accelerator.

-Rick Cosnett - "Eddie Thawne" - based on the DC Comics character Professor Zoom. A recent transfer to the Central City Police Department, Thawne's past is a mystery and harbors a dark secret.

-Jesse L. Martin - "Detective West" - a cop who acts as a surrogate father to Barry and is the father of Iris West.

-Danielle Panabaker - "Caitlin Snow" - based on the DC Comics character Killer Frost. A highly intelligent bioengineering expert, Snow lost her fiancé during an explosion at S.T.A.R. Labs.

-Candice Patton - "Iris West" - daughter to Detective West and best friend to Allen.

-Carlos Valdes - "Cisco Ramon" - based on the DC Comics character Vibe. A mechanical engineering genius, Ramon is the youngest member of the team of scientists at S.T.A.R. Labs.

-Chad Rook - "Clyde"