Braugher had a prolific career in television and film dating back more than 30 years and highlighted by multiple award nominations and wins.
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His representative confirmed to ABC News that he died Monday. Details on the nature of his illness were not disclosed.
Braugher was known as a powerful and intense presence as Detective Frank Pembleton on "Homicide" in the late 1990s - a role for which he won an Emmy.
He later shifted to comedy - again in a police role on "Brooklyn Nine-Nine" but with a comic, deadpan spin as Captain Raymond Holt, the commanding officer who never cracked a smile in the face of Andy Samberg's antics.
The Chicago-born actor had his breakthrough role in "Glory," starring alongside Denzel Washington and Morgan Freeman in the 1989 film about an all-Black regiment during the Civil War.
He won his second Emmy, for lead actor in a miniseries or movie, for the 2006 limited series "Thief." He was nominated for 11 Emmys overall in his career.
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He made appearances in dozens of other films, including "Primal Fear," and "Salt." He also lent his voice to animated roles in TV's "BoJack Horseman" and "Superman/Batman: Apocalypse."
Braugher is survived by his wife, Ami Brabson - his "Homicide" costar whom he married in 1991 - and their three children.
Tributes were being posted on social media by friends and former costars.
Terry Crews, who costarred on "Brooklyn Nine-Nine," wrote on Instagram: "Can't believe you're gone so soon. I'm honored to have known you, laughed with you, worked with you and shared 8 glorious years watching your irreplaceable talent. This hurts. You left us too soon."
And Marc Evan Jackson, who played Holt's husband on the sitcom, posted a picture with Braugher captioned "Oh Captain. My Captain."
The Associated Press and ABC News contributed to this report.