The parcel is next door to First Niagara Center.
The Sabres' project will include two ice rinks, a hotel, a restaurant, retail outlets, and a parking ramp, Brown said in his remarks outside the arena.
The project will require the work of about 1,500 construction personnel, Brown said.
"Up to 350 full time jobs will be created," he added.
Work on the project is set to begin next Spring, the mayor said. The rinks, retail outlets, the restaurant and the parking ramp should be complete in 2014, and the hotel should be ready to welcome guests in 2015.
Terry Pegula says he had this project in mind when he bought the team.
"To help the area ... help some employment," Pegula said.
Pegula said he got the idea from seeing similar work done in Pittsburgh, which helped that city refine its image as a community focused solely on the steel industry. He also hopes the project will excite future draft picks for the Sabres, especially on draft day.
"A bunch of young guys sitting up in the stands saying, c'mon, please, please ... so, doing things like this starts you down that road," Pegula said.
The city chose the Harbor Center project over another proposal from Carl Paladino's Ellicott Development firm.