It is the 1940s as Garrison Yokum grows up in Betsy Layne, Kentucky. He enjoys sitting on the back porch with his cousins, watching trains haul coal to big cities, dreaming of what lies beyond the mountains, and traveling along the "big road," also known as US Route 23, with his parents on Saturdays. But when Garrison is seven, work becomes even more difficult, dangerous, and precarious for his coal miner father, setting into motion a chain of events that ultimately leads them to Ann Arbor, Michigan, for a new life. From that point on, Route 23 becomes a focal point in Garrison's life.

Decades later and now approaching retirement, Garrison makes another life-changing decision as he nears completion of a documentary on the migration of families from rural east Kentucky to the cities along Route 23. After he sets out on a road trip with his professional photographer granddaughter and two student interns, Garrison explores and captures life along the long, important American highway that helped many families secure better futures beyond the mountains of southern Appalachia.

The Big Road is a generational story that documents the experiences of those who migrated from southern Appalachia to bigger cities in the north by way of a memorable American highway.