Set in Los Angeles, "Sangre Negra" aka "Black Blood' is the cross-generational saga of the wealthy Santos family. It blends the style of classic TV series like "Dallas", The Sopranos" and "Dynasty", with the contemporary Latin feel of TV series "Queen of the South", "Narcos", and "Power ". Led by patriarch Guillermo Santos Sr. (Erik Estrada), and his sons; the slick defense attorney Guillermo Santos Jr., (Ricardo Herranz), the decorated police detective Christian Santos (Danny Arroyo), and the illegitimate son and gangster "Pretty" Ricky Santos (Antonio McKay). Ricky infuriates his "law and order" blood family by joining the notorious Sabatini crime mob family, led by Guillermo Sr.'s long time nemesis, Vinnie Sabatini (Robert Miano). Christian is engaged to beauty queen Francesca Natal (Arianna Gomez), the mother of Ricky Santos' daughter, Natalya. Laura Santos (Sandra Santiago) is the glamorous, but vindictive 2nd wife of Guillermo Sr. College student Miguel Santos (Angel Garet), nephew to the Santos brothers, finds himself drawn into Ricky's flamboyant underworld lifestyle, that includes disgraced former Navy Seal Ike Rollins (Billy R. Smith), and career criminal Cimarron Squalley (Stoney Jackson).

Vinnie discovers Rick's plan and sets out to beat him at his own game. Guillermo Jr. decides to run for State's Attorney of California. Francesca is torn between her love for Christian and her feelings for Ricky. Ricky initiates his plan.