[4] While she was in high school, she decided she wanted to be an actress; in 1994, she graduated from the Aleksander Zelwerowicz National Academy of Dramatic Art in Warsaw.

[6] She made her big screen debut playing the leading role in the Polish comedy-drama film Człowiek z... directed by Konrad Szołajski.

[6] On television, Kulesza starred alongside Magdalena Walach and Marzena Trybała in the Polsat drama series, Pensjonat Pod Róza (2004—2006) about three women in small hotel.

In 2008 Kulesza, alongside her professional partner Stefano Terrazzino, won the eighth series of Dancing with the Stars: Taniec z gwiazdami.

[8] In 2009 she starred in the short-lived sitcom Synowie and in 2011 was a regular cast member in the telenovela Prosto w serce, a remake of Argentine series, You Are the One.

Suicide Room premiered at the 62nd Berlin International Film Festival and received positive reviews from critics while Kulesza's performance was noted.

[15] Kulesza won her first Polish Academy Award for Best Actress for her role Róża, a Masurian widow who falls in love a Home Army soldier.

Playing Wanda Gruz, a Communist resistance fighter turned state prosecutor, Kulesza received widespread acclaim.

[18][19] David Denby from The New Yorker noted that "Wanda tells her of her past in brief fragments, and Kulesza does more with those fragments—adding a gesture, a pause—than anyone since Greta Garbo, who always implied much more than she said.

"[20] Dana Stevens wrote that "As played, stupendously, by the veteran Polish TV, stage, and film actress Agata Kulesza, Wanda is a vortex of a character, as fascinating to spend time with as she is bottomlessly sad.

"[21] Jose Solis from PopMatters named her Best Supporting Actress writing: "Kulesza also allows her character’s flaws to show in heartbreaking ways, especially when we least expect it to.

She co-starred opposite Bartłomiej Topa in the crime drama film Traffic Department (2013), the romantic comedy Wszystkie kobiety Mateusza (2013), the period LGBT-romantic thriller In Hiding (2013), the drama The Mighty Angel (2014), the action thriller Secret Wars (2014) and the comedy film All About My Parents, for which she received another Polish Academy Award nomination for Best Actress.

[31] Film critic Stephen Holden from The New York Times wrote: "The most complicated and compelling character is the severe Mother Abbess, who faces an excruciating choice between saving a baby’s life and risking disgrace, or abandoning the infant.

Despite some praise for the cast, critics panned Dark Crimes for its pacing, overly downcast tone, and objectionable presentation of abused women.

[42][43] In 2020, Kulesza starred in five movies: the social thriller The Hater directed by Jan Komasa, the comedy-drama Never Gonna Snow Again by Małgorzata Szumowska and Michał Englert, the crime Western Magnesium by Maciej Bochniak, the dance drama Parquet by Aleksandr Mindadze, and the prison drama 25 Years of Innocence by Jan Holoubek.

In Never Gonna Snow Again she played wealthy drug-taking widow,[46][47] for which she received another Polish Academy Award nomination for Best Actress.

[51] Later in 2021, Kulesza began starring in the Player.pl crime drama series, The Convict playing the role of Judge Alicja Mazur who accused of a murder she did not commit.

[62] Later in 2024, Kulesza was cast opposite Joanna Kulig as Dr. Bożena Hager-Małecka in the Netflix miniseries, Olowiane dzieci about 1974 lead poisoning epidemic in Poland.