Sidse Babett Knudsen made her first screen appearance as ‘Mercedes’ in the 1995 television comedy-drama series, ‘Juletestamentet.’ She made her silver screen debut in the 1997 Danish film ‘Let's Get Lost’ directed by Jonas Elmer. Knudsen played the role of ‘Julie’ in the film which earned her the ‘Bodil Award’ and the ‘Robert Award’ for Best Actress. In 1998, she became a part of the Danish television series ‘Strisser på Samsø.’ She played the role of ‘Hanne Jensen’ and appeared in 2 episodes of the show. Knudsen became a second-time recipient of both the ‘Bodil Award’ and the ‘Robert Award’ for her performance as ‘Sus’ in the 1999 Susanne Bier-directed Danish romantic comedy film, ‘The One and Only.’ The film became one of the highest-grossing Denmark films of the 1990s. The same year, she also appeared in the romantic comedy film ‘Mifune’ which was also a major commercial success. Knudsen was next seen in films like ‘Mirakel’ (2000), ‘Chop Chop’ (2001), ‘Drengen der ville gøre det umulige’ (2002), ‘Se til venstre, der er en svensker’ (2003), and ‘Villa Paranoia.’ In 2006, she starred as ‘Helene Hansson’ in the Danish-Swedish drama film ‘After the Wedding’ directed by Susanne Bier. The film was a critical and commercial success and earned an Academy Award nomination for Best Foreign Language Film. Knudsen also received the ‘Rouen Nordic Film Festival Award’ and ‘Zulu Award’ for her performance in the film.
She continued to star in films like ‘Til døden os skiller’ (2007), ‘Blå mænd’ (2008), ‘Over gaden under vandet’ (2009), ‘Æblet & ormen’ (2009), and ‘Parterapi’ (2010). In 2010, she joined the cast of the Danish political drama television series ‘Borgen’ as ‘Birgitte Nyborg.’ The series completed its fourth season in 2022. Knudsen was next seen in films like ‘Sover Dolly på ryggen ?’ (2012), ‘The Duke of Burgundy’ (2014), ‘Speed Walking’ (2014), ‘Courted’ (2015), ‘150 Milligrams’ (2016), ‘Inferno’ (2016), ‘A Hologram for the King’ (2016), ‘The Eternal Road’ (2017), ‘In Fabric’ (2018), and ‘The Translators’ (2019). Knudsen made her last big-screen appearance in the 2020 British comedy-drama film ‘Limbo’ directed by Ben Sharrock. The film received a positive response from critics.