J. D. Pardo as Ezekiel "EZ" Reyes, a prospect at the beginning of the series, promoted to Vice Presidente then Presidente of the Mayans M.C., Santo Padre Charter. He joined the club following his release from prison. He is the younger brother of fellow club member Angel Reyes, who sponsored him during his time as a prospect, and is the son of Felipe and Marisol Reyes.
Clayton Cardenas as Angel Reyes, a full patch member and later El Secretario (Secretary) of the Mayans M.C., Santo Padre Charter. He is the older brother of EZ and the son of Felipe and Marisol.
Sarah Bolger as Emily Galindo (née Thomas), EZ's former childhood sweetheart, now the wife of Miguel Galindo and the mother of their son, Cristóbal Galindo II, who is named after Miguel's deceased brother. She is also the older sister of Erin Thomas.
Michael Irby as Obispo "Bishop" Losa, the former Presidente and Vice Presidente of the Mayans M.C., Santo Padre Charter. He is one of the three Kings of the Mayans M.C. and cousins with its founder Marcus Alvarez. He had a young son with Antonia Pena, Aidan Losa, whose death from a car accident continues to haunt him.
Carla Baratta as Luisa "Adelita" Espina, who as a child watched her family die at the hands of the Galindo Cartel. She is the former leader of Los Olvidados (The Forgotten Ones), a group of Mexican rebels who are devoted to fighting the Galindo Cartel.
Richard Cabral as Johnny "El Coco" Cruz (seasons 1–4), a former Marine sniper and a full patch member of the Mayans M.C., Santo Padre Charter. He is the father of Leticia Cruz and the son of Celia.
Raoul Max Trujillo as Che "Taza" Romero (seasons 1–4; guest season 5), a former Vice Presidente of the Mayans M.C., Santo Padre Charter. He was also a former member of the Vatos Malditos M.C. but left after its president, El Palo, killed his own brother David, with whom Taza was in a secret relationship.
Antonio Jaramillo as Michael "Riz" Ariza (seasons 1–2), a Santo Padre local and Él Secretario of the Mayans M.C., Santo Padre Charter. He is also the nephew of Vicki Ariza.
Danny Pino as Miguel Galindo, the former leader of the Galindo Cartel, a Mexican drug cartel, who took over leadership following the death of his father, and cartel founder, Jose Galindo. He's the husband of Emily, the father of their son Cristóbal, the son of Jose's widow Dita Galindo and the biological son of Felipe Reyes.