Hirosue made her television debut in 1995 at the age of 15 in Fuji TV's Heart ni S. She was also named "Best Newcomer" at the 10th Television Drama Academy Awards the same year when she starred in Fuji TV's comedy series, Shota no Su Shi. In 1997, she appeared in the finalé of medical drama, Hoshi no Kinka and the special episode of Odoru Daisousasen before making her breakthrough performance in Fuji TV's comedy series Beach Boys, where she was awarded "Best Supporting Actress" at the 14th Television Drama Academy Awards. Hirosue also made her film debut in the same year when she appeared in 20-seki Nostalgia which won her critical acclaim. She was awarded the Sponichi Grand Prize New Talent Award at the Mainichi Film Awards, Best New Talent at the Yokohama Film Festival and perhaps most importantly, the Newcomer of the Year award at the 21st Japanese Academy Awards.

In 1998, Hirosue reprised her role in the special episode of Beach Boys while also appearing in four other television dramas in the same year. In 1999, she returned to the big screen in Poppoya and Himitsu. Her performances in both films won her much praise from award-giving bodies of Japan and she received two nominations at the 23rd Japanese Academy Awards for Best Actress (for Himitsu) and Best Supporting Actress (for Poppoya). Her international profile also increased when she received the Best Actress prize for her performance in Himitsu at the 30th Sitges - Catalan International Film Festival.

She returned prominently to television in 2000 playing Yuki Katase in the drama Summer Snow, which won 5 awards at the 26th Television Drama Academy Awards including "Best Supporting Actress" and "Best Drama" before showing off her comedic chops in TBS's Oyaji. The latter role again won her "Best Supporting Actress" at the 27th awards ceremony.

In 2001, Hirosue made her international film debut in Luc Besson's Wasabi. Not being able to speak French for her role, she had to learn her lines phonetically. She also reunited for the fourth time on television with her frequent co-star, Yutaka Takenouchi (they starred together in Long Vacation, Beach Boys and Seikimatsu no Uta), in Fuji TV's romantic comedy series Dekichatta Kekkon, starring as an expectant couple who did not know each other well before their one-night stand leading to the planning of a shotgun wedding. The series also starred Hiroshi Abe who won Best Supporting Actor at the 30th Television Drama Academy Awards.

In 2002, Hirosue appeared in the film Renai Shashin and the low-rated television drama, Ai Nante Irane Yo, Natsu before capping the year in the family drama series, Otousan. She reunited with her Summer Snow lead co-star, Tsuyoshi Dōmoto, in 2003's romance series Moto Kare. Her portrayal as the initially flippant ex-girlfriend, Makoto Saeki, won her "Best Supporting Actress" yet again at the 38th Television Drama Academy Awards.

Hirosue married model Takahiro Okazawa on January 17, 2004 and gave birth to her son on 10 April 2004. They later divorced in March 2008. Her marriage and new motherhood decreased her workload when she only made one appearance in 2004 in the film, Hana and Alice, and in 2005's Fuji TV's romance drama, Slow Dance.

Hirosue returned to film and television in 2006 by appearing in three television dramas, a TV movie and a film. In 2007, she co-starred for the third time with Hiroshi Abe (her fellow actor in Dekichatta Kekkon and Haruka Naru Yakusoku) in the film, Bubble Fiction: Boom or Bust. She also appeared in two TV movies, Mama ga Ryori o Tsukuru Wake, aired by Fuji TV and Long Wedding Road! which was broadcast by TBS. Hirosue also made a guest appearance in the third episode, Rattles, of detective-mystery series, Galileo.

She portrayed Mika Kobayashi opposite Masahiro Motoki in the 2008 Japanese film Departures, which won the 81st Academy Awards Best Foreign Language Film.

In 2009, she is starring in the remake of the mystery film Zero Focus and the adaptation to film of the novel Villon's Wife by Osamu Dazai.

She has a son born on 2004 from her previous marriage. On October 9, 2010 she married Jun Izutsu, a candle Artist. They met in Haiti in March 2010 participating in earthquake relief efforts. She has two sons. Her cousin is a former member of the House of Representatives in Japan. On July 17, 2015, she gave birth to her third child, a girl.