Powell, who had been receiving treatment at Walter Reed National Medical Center, died at the age of 84, his family said in a statement on social media.
Colin Powell, the first Black US secretary of state and top military officer, has died at the age of 84 due to complications from Covid-19.
He was fully vaccinated, his family said in a statement on Facebook.
"We have lost a remarkable and loving husband, father, grandfather and a great American," his family said.
Powell was one of America's foremost Black figures for decades.
He was named to senior posts by three Republican presidents and reached the top of the US military as it was regaining its vigor after the trauma of the Vietnam War.
Powell, who was wounded in Vietnam, served as US national security adviser under President Ronald Reagan from 1987 to 1989.
As a four-star Army general, he was chairman of the military's Joint Chiefs of Staff under former president George HW Bush during the 1991 Gulf War in which US-led forces expelled Iraqi troops from neighboring Kuwait.
Moderate and pragmatist
Tributes nevertheless poured in from Congress, where Democratic Senator Mark Warner praised Powell as "a patriot and a public servant," while House Republican Peter Meijer described him as a rarity in the modern age: "a true soldier statesman."
Powell, a moderate Republican and a pragmatist, considered a bid to become the first Black president in 1996 but his wife Alma's worries about his safety helped him decide otherwise.
In 2008, he broke with his party to endorse Democrat Barack Obama, who became the first Black elected to the White House.
Powell will forever be associated with his controversial presentation on February 5, 2003, to the UN Security Council, making former president George W Bush's case that Iraqi president Saddam Hussein constituted an imminent danger to the world because of his stockpiles of chemical and biological weapons.
Powell admitted later that the presentation was rife with inaccuracies and twisted intelligence provided by others in the Bush administration and represented "a blot" that will "always be a part of my record".