
Pada 1991, melejitnya lagu Cobain yang paling terkenal, Smells Like Teen Spirit, menandai bermulanya perubahan besar dalam musik pop dari jenis musik yang populer pada tahun 1980-an seperti glam metal, arena rock, dan dance-pop menjadi grunge dan rock alternatif. Selain itu lagu-lagu tulisan Cobain lainnya misalnya About a Girl, Come as You Are, In Bloom, Lithium, Heart-Shaped Box, All Apologies, dan Rape Me.
Pada 1 Maret 1994, setelah konser di München, Jerman, Cobain didiagnosa dengan bronkitis dan laringitis yang parah. Ia diterbangkan ke Roma hari berikutnya untuk menjalani pengobatan, dan istrinya bergabung pada 3 Maret. Pagi berikutnya, Love bangun dan menemukan Cobain dilarikan ke rumah sakit dan setelah lima hari di sana diperbolehkan pulang. Cobain dimasukkan ke panti rehabilitasi pada tanggal 30 Maret. Pada malam 1 April, Cobain keluar untuk kabur dari panti tersebut dengan memanjat pagar. Ia kemudian pergi ke Seattle dan menghilang.
Pada tanggal 3 April, Love menghubungi seorang penyidik swasta bernama Tom Grant, dan menyewanya untuk menemukan Cobain. Pada tanggal 8 April 1994, jenazah Cobain ditemukan di sebuah ruangan di atas garasi rumahnya di Lake Washington oleh pegawai Veca Electric bernama Gary Smith. Otopsi kemudian memperkirakan Cobain tewas pada 5 April 1994.

After signing with major label DGC Records, the band found breakthrough success with "Smells Like Teen Spirit" from their second album Nevermind (1991). Following the success of Nevermind, Nirvana was labeled "the flagship band" of Generation X, and Cobain hailed as "the spokesman of a generation". Cobain, however, was often uncomfortable and frustrated with that label, believing his message and artistic vision to have been misinterpreted by the public, with his personal issues often subject to media attention.
During the last years of his life, Cobain struggled with addiction, chronic health problems and depression. He also had difficulty coping with his fame and public image, and the professional and personal pressures surrounding himself and his wife, musician Courtney Love. On April 8, 1994, Cobain was found dead at his home in Seattle, the victim of what was officially ruled a suicide by a self-inflicted shotgun wound to the head. The circumstances of his death at age 27 have become a topic of public fascination and debate.
Since their debut, Nirvana, with Cobain as a songwriter, has sold over 25 million albums in the U.S., and over 75 million worldwide. Cobain was posthumously inducted into the Rock and Roll Hall of Fame in 2014, along with Nirvana bandmates Krist Novoselic and Dave Grohl, in their first year of eligibility.