Sidse played the lead character in Susanne Bier's 1999 romantic comedy The One and Only. The film became one of the decade's biggest box-office hits in Denmark. It marked a new direction in modern Danish romantic comedies with credit given to Sidse's acting style. She again earned both the Robert Award and the Bodil Award for Best Actress.
In 2006 Sidse Babett received nominations for her lead in Susanne Bier’s After the Wedding. The film was nominated Academy Award for Best Foreign Language Film, and Sidse won, among others, for Best Actress at the Rouen Nordic Film Festival.
Sidse Babett has had great success, in Denmark and abroad, for the lead as Prime Minister Birgitte Nyborg in the critically acclaimed Television Drama-series Borgen, for which she also received the Golden Nymph Award as Outstanding Actress in Monte Carlo 2011 and a BAFTA in 2012.
Sidse has also starred in two French feature films L’Hermine for which she received the French César award, and La Fille de Brest that will open on Toronto film festival in September 2016.
Internationally Sidse’s first foreign project was the lead in the UK feature The Duke of Burgundy directed by Peter Strickland then feature film from German director Tom Tykwer, A Hologram for the King and soon she is to be seen in Ron Howard's Inferno.