Born in Witten/Ruhr as the child of two doctors working in development aid, she grew up in Liverpool (England), Kowloon (Hong Kong), Densapar, Bali (Indonesia) and Biersdorf in the Eifel region.

In 1992, after her acting studies at the Otto Falckenberg Schule in Munich, she took up her first engagement at the Staatstheater Hannover. In 1993, she moved to the Bayerische Staatsschauspiel München. This is where her intensive collaboration with Andreas Kriegenburg began. In 1998 she was voted Actress of the Year. This was followed by an engagement at the Vienna Burgtheater in 1999. From 2002 to 2009, Natali Seelig was a member of the ensemble at the Thalia Theatre in Hamburg, where she appeared in plays by Armin Petras, Jorinde Dröse and Alice Zandwijk, among others.

Natali Selig has been a member of the ensemble at the Deutsches Theater Berlin since the 2009/10 season. Since then she has appeared in productions by Lilja Rupprecht, Philipp Arnold, Tom Kühnel and Jürgen Kuttner, Jan Bosse, Anne Lenk and many more.