Growing up in Vault 101, Isaac had his entire life planned out for him - predictable, unremarkable and, above all, safe. When his father disappeared from Vault under mysterious circumstances, however, he set in motion a series of events which ended with the Vault Overseer dead and Isaac banished to the ruins of Washington D.C. Tales of the melancholic "Lone Wanderer" - artless, selfless, and apparently capable of performing miracles - soon spread throughout the Capital Wasteland, as Isaac helped reclaim the National Mall with the Brotherhood of Steel, engineered the downfall of Eulogy Jones at Paradise Falls, and opposed the Enclave over the Jefferson Memorial. Throughout it all Isaac was just trying to locate his father, and return them both to the Vault where they belonged.
Isaac's father eventually met his end at the hands of the Enclave, and left behind his life's work on "Project Purity" - an audacious plan turn the Potomac River into clean, potable water, with the help of a Garden of Eden terraforming device. With assistance from the people of Rivet City, Isaac eventually recovered the device from Vault 87 and steeled himself to enter the radiation-filled purifier chamber. However, his friend and mentor, Brotherhood Sentinel Sarah Lyons, chose to lay down her life instead. Isaac's role in Lyons' death made him instant persona non grata amongst the remaining East Coast chapter, and he briefly retreated to Rivet City. Whilst there he became embroiled in a mystery involving a "synth" impostor - one which put him in contact with the Railroad and, ultimately, his route out of the Capital Wasteland.
Since then Isaac has been operating as a Railroad agent across the east coast, under the codename "Wanderer". Polite but distant, few are aware that the enigmatic Wanderer is also the tender-hearted savior of Washington D.C. - or so Isaac thought. When the Brotherhood command center appears in the skies above Massachusetts, along with its wunderkind leader Arthur Maxson, it soon becomes apparent that somebody is feeding information about him that could threaten the Railroad's very existence. Isaac has spent his adult life trying to outrun the sins of his past. Now, it seems his judgement may finally be at hand.