Miguel H. Trujillo was born on April 30, 1904, at the Pueblo of Isleta, in New Mexico to Juanita (née Jaramillo) and José Trujillo.  José was a farmer, but died when Trujillo was seven years old, leaving Juanita to raise their four children. Both Trujillo and his older brother, Manuel, known as "Bob", took odd jobs to help until they were old enough to go to school.  He attended the Albuquerque Indian School until the tenth grade and then went to high school at the Haskell Institute in Lawrence, Kansas.  Eventually, he earned a bachelor's degree from the University of New Mexico.

He later went on to become an activist, who was instrumental to the case Trujillo v. Garley in 1948; before the case, New Mexico, like many other states, had a ruling that "Indians not taxed" were not legally allowed to vote. With the case Miguel successfully challenged this ruling.