Death is one of the Horsemen of the Apocalypse, alongside War, Famine, and Pestilence. In the episode "Abandon All Hope...," Death is revealed to be imprisoned deep within the earth. He is also referred to by Bobby Singer as "the Big Daddy Reaper," suggesting that he created the race of Reapers. Later, Lucifer performs a ritual that frees Death from his prison.
In "Dead Men Don't Wear Plaid," Death is revealed to be responsible for causing the dead in Sioux Falls, North Dakota to rise. Bobby's resurrected wife describes Death as a thin, skeletal man.
In "Two Minutes to Midnight," Death comes to Chicago, where a massive storm is about to devastate the city; he is shown driving a white car. After he exits his car and as he makes his way down a sidewalk, a passerby bumps into him and rudely tells him to watch where he's going; this prompts Death to brush the spot the passerby touched him and cause the passerby to drop dead. Later, Death is sitting in a restaurant eating pizza when Dean Winchester sneaks in, intending to kill the Horseman with his own scythe so he can obtain his ring (one of four needed to open Lucifer's cage). Unfortunately, Death's scythe burns in Dean's hand, causing him to drop it. Death, however, simply thanks Dean for returning his scythe (which suddenly appears on the table next to Death) and invites him to sit down for some pizza.
Dean complies, and the two engage in a conversation in which Death claims to be either as old as God or even older, then states that he'll eventually reap God Himself, much to Dean's shock. Death then goes on to explain that Lucifer used a spell to bind him (Death) to his control, using Death to cause all matter of disasters (among them floods, earthquakes, raising the dead), and expresses his displeasure with Lucifer (whom he characterizes as a "child throwing a tantrum"). That said, he then offers Dean his ring on the condition that Dean allows Sam to consent to Lucifer possessing him so he can jump into Lucifer's cage. After a moment, Dean agrees, and Death hands over his ring, then gives Dean the instructions on using the Horsemen rings.
Death returns in the Season 6 episode "Appointment In Samarra." While Dean argues with the Reaper Tessa whilst attempting to summon Death, Death himself appears. Dean then, much to Death's annoyance, briefs him about Sam's soul being left in Lucifer's cage along with Adam Milligan, the Winchesters' half-brother. When asked to retrieve Sam's soul and Adam from the cage, Death forces Dean to choose between the two; Dean chooses Sam's soul. Death agrees to put up a mental barrier in Sam's mind to keep him from remembering his time in Hell, provided that Dean agrees to act as him (Death) for a day by putting on his ring. Although Dean ultimately fails the test, Death nonetheless retrieves Sam's soul. Before restoring Sam's soul and erecting the barrier in Sam's mind, he warns Sam to not "scratch the wall," stating that he won't like what he will see.
Death next appears in "Meet the New Boss," the Season 7 premiere. After Castiel absorbs all the souls in Purgatory and becomes the new "God," Dean, Sam, and Bobby summon the demon Crowley to ask for a means to bind Death to their control, recalling that Lucifer had done the same thing. Crowley delivers the spell, which the three hunters cast. Not long after, Death appears and initially assumes that the Winchesters bound him in the hopes of getting him to fix the broken mental barrier in Sam's mind (the barrier had been broken earlier by Castiel), but is told by Dean that they want him to kill Castiel; Death then states he can't fix the wall.
Castiel suddenly appears, angered at what he perceives as betrayal on part of the Winchesters and Bobby. Death proceeds to mock Castiel, calling him a "mutated angel," and then reveals that Castiel not only absorbed the souls in Purgatory but also the Leviathan, God's earliest creations (whom Death states he found "entertaining"). Death and Castiel then have a brief but tense verbal exchange in which Death states that Castiel is no god. A fed-up Dean then orders Death to kill Castiel, and Death is about to oblige when Castiel frees him from the binding spell. After Castiel disappears, Death states he had a tingle he'd reap someone that day, then sits down and starts to slowly eat a meal of pickled chips and soda. Once finished eating, Death coldly chastises Dean for not stopping Castiel earlier. Nonetheless, he agrees to cause an eclipse so the Winchesters and Bobby can use the spell to open Purgatory again. Before leaving, Death threatens to kill the Winchesters and Bobby if they try to bind him again.