Eventually, the convent's true nature was discovered by the Yellow-Eyed Demon, Azazel. The convent was attacked by Azazel himself upon this discovery, resulting in a bloody massacre that resulted in the closing and abandonment of the convent. Several decades later, it was the site of Lucifer's release after the sacrifice of Lilith by a special child spoken of in prophecy by Lucifer himself, Sam Winchester.
In 1972, the demon Azazel, after many supposed years of searching, discovered the location of his "father," Lucifer's, prison to be in a prominent convent in Ilchester, Maryland, St. Mary's Convent. The convent was home to a colony of nuns and tended to by a chief priest who oversaw the caretaking tasks of the church. Azazel journeyed to this place and took possession of the priest's body, entering him and forcing him to do his bidding. The possessed priest then conducted a mass in the main hall of the convent, with the convent's eight nuns all in attendance. It soon became apparent that something was odd about the priest's behavior, as he casually skipped several parts of the Lord's Prayer and paused several times. He soon began to muse about searching for many long years for his "father", who had been put "in jail" by God. After several minutes of talking about his search and his discovery that Lucifer's prison was upon the very ground which now stood a convent, as well as the irony of the location, the priest, now revealed to be Azazel, picks up a knife from the altar and proceeded to disembowel all of the nuns, whom he had locked inside the room.
After all of the nuns were killed, the main hall of the convent was left a bloody mess, Azazel (still possessing the priest) laid the corpse of one of the nuns flat upon the altar and prayed to Lucifer, entreating him to "whisper through the door" to him. A strange breeze blew through the room, and the nun's body lying on the altar gasped and began to speak in a demonic voice, the voice of Lucifer himself. Azazel stated his relief at finally hearing Lucifer's voice again and reiterated his ultimate loyalty to Lucifer, to which Lucifer replied that he "had done well". Azazel then requested the knowledge of how to break Lucifer out of his prison, to which Lucifer replied with one word: "Lilith". Azazel reminded his father that Lilith was, at that time, "trapped neck-deep in the pit "of Hell, as well as reiterating how difficult it would be to release her from the pit without anyone noticing. Lucifer reiterated her importance to his release however and stated that she could break the Seals binding him in his prison. Azazel affirmed that he would seek a way to break Lilith out of Hell as per Lucifer's order, but he also asked what he himself should do to ensure Lucifer's release. Lucifer responded with his request that Azazel find him a "very special child", one that would possess great psychic powers and that would be powerful enough to perform the deed of sacrificing Lilith and thus ensuring his release.
After his conversation with Lucifer, Azazel left to set his plans into motion to fulfill Lucifer's orders and ensure his release by finding a way to break Lilith out of Hell. However, most of Azazel's work was finding a special child that could sacrifice her. Once Azazel left his meatsuit, the priest was captured and interrogated by the authorities as to the bloody massacre of St. Mary's he had seemingly orchestrated. The priest stated that he had been forced to perform the terrible deeds by a demon named Azazel and that he was not at fault for the bloodbath. Following this, St. Mary's Convent was abandoned and largely forgotten by the mainstream public, but it continued to be a place of importance over the years for Azazel and his associates.
The convent was revisited, 37 years after its abandonment, in 2009 by the now-released Lilith (who escaped through the Devil's Gate when Azazel arranged its opening). Lilith had already led to the breaking of 65 of the 66 seals and, knowing Sam Winchester would soon pursue her to this place, prepared to meet her fate and ensure her creator's release from Hell. Sam Winchester arrived soon after with the demon, Ruby. The pair confronted Lilith in the main chamber where Azazel's murder of the nuns had taken place 37 years earlier, with Sam telekinetically throwing Lilith against the altar and pinning her there before using his enhanced demonic powers to kill her, not realizing that her death was the final Seal. Soon after, Ruby was killed by Dean Winchester after she was revealed to be a traitor working with Lilith all along.
As Lilith's blood poured from her mouth, it formed a circle in the middle of the chamber and began to spin, opening the gates of Lucifer's prison and enabling Lucifer to rise once more to wreak havoc upon the world.
As the gateway to Hell opened, the Winchester brothers were trapped in the chapel as Lucifer began to rise, but just as all seemed lost for the brothers, God himself intervened to transport them safely onto a plane flying over Ilchester, from which they watched in horror, the start of the Apocalypse as a blast of brilliant white light shot up into the sky from where St. Mary's Convent stood. The chapel was later mentioned to have been completely obliterated by the Devil's unleashed presence. During a radio broadcast that Sam and Dean heard on the car's radio a few hours later the local authorities deemed that it was not a terrorist attack but an explosion that destroyed the Chapel.