Miller received local training in Baltimore and studied portraiture with Thomas Sully in Philadelphia (1831–1832). He furthered his education in France (1833-1834) at the École des Beaux-Arts in Paris and in Italy at the English Life School in Rome. His Baltimore studio was initially unsuccessful. 

In 1836, in his new New Orleans studio, Miller met Captain William Drummond Stewart, a Scottish aristocrat and British Army officer. Stewart hired Miller to accompany him on a 1837 trip to the Rocky Mountains to create sketches for oil paintings for his Scottish castle. 

The approximately 200 resulting sketches and notebook studies, primarily from Southwestern Wyoming, offered psychological insight into mountain men and Indians, capturing the end of the mountain men's heyday. These works were intended for Stewart's private enjoyment, not public display. 

Miller lived at Stewart's ancestral home, Murthly Castle in Scotland, from 1840 to 1842, fulfilling his commitment by painting the oil scenes from their journey. 

Settling back in Baltimore, Miller made a good living from numerous copies of his Rocky Mountain sketches and from portraiture. He often supplied narrative descriptions with his paintings but, unlike many other Eastern travelers, never published written descriptions of his western adventures.