Brooke, who represented Massachusetts from 1967-1979 in the US Senate, championed laws to benefit the disadvantaged during his two terms.
President Barack Obama hailed his "extraordinary life of public service."
"Ed Brooke stood at the forefront of the battle for civil rights and economic fairness," said Obama, America's first African American president in a statement.
"During his time in elected office, he sought to build consensus and understanding across partisan lines, always working towards practical solutions to our nation's challenges."
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Born October 26, 1919, Brooke served in the US Army during World War II, fighting in Italy as part of the all-black 366th Infantry Regiment and earning a Bronze Star.
A liberal Republican who grew up in racially divided Washington, Brooke served in the 100-seat US Senate for two terms.
Before Brooke, other African Americans had served in the Senate but they were chosen by state legislatures rather than elected by popular vote.
Brooke was also awarded the Presidential Medal of Freedom, and has received honorary degrees from more than 30 colleges and universities.
Brooke studied at Howard University in Washington and practiced law.
Before joining the Senate, he was the attorney general for Massachusetts. He was the first black person to hold a state attorney general post in the US.
"Senator Brooke's accomplishments remind us that anything is possible in our country," said Senate Republican leader Mitch McConnell.
Secretary of State John Kerry, a former Democratic senator, agreed.
"Ed Brooke: trailblazer, gentleman, public servant personified. Guts and integrity. God bless," he wrote on Twitter.