The 44-year-old Democrat is seeking a seat left vacant by the death on Monday of the oldest US senator, Frank Lautenberg, a Democrat.
A special election to fill the seat has been set for October 16 by Republican Governor Chris Christie, who has convened party primaries for August 13.
"I'm running because I believe that people who care can find solutions to even the most difficult challenges," Booker said, promising "promising pragmatism over partisanship."
He spoke at a news conference in Newark, the crime-ridden, trouble plagued New Jersey city that Booker has tried to turn around since being elected mayor in 2006.
Booker had already planned to run in the 2014 mid-term elections, and had raised $1.9 million by the end of the last reporting period in March, according to electronic filings.
He is considered an early frontrunner in a Democratic primary race against Representative Rush Holt, who had just under USD 800,000 in campaign coffers in March.
Frank Pallone, a Democratic congressman with strong support from unions, is also expected to enter the contest. He had USD 3.7 million on hand by the end of March.
Democrats have only a five seat majority in the 100-seat US Senate, ensuring the race will be a fiercely contested prelude to the mid-term elections, when 35 of the chamber's seats will be up for grabs.
Last year, he made headlines by rescuing a woman from a burning house, and in 1999 drew attention with a 10-day hunger strike to protest drug smuggling.
He lived in a motor home the following year, parking it on the city's most drug-infested corners to encourage fellow residents and businesses to fight against crime and drug dealing.
A former All-American football player, he has been nicknamed "The Savior of Newark" for his efforts targeting inner-city problems.