The 79-year-old resident of Rensselaer County near Albany said he would like to return to the private sector and run a business.
State law prohibits him from a lucrative job of lobbying the Legislature for two years.
Republican Sen. Dean Skelos of Long Island has been chosen to replace Bruno, with Bruno's support.
In the two years since Gov. George Pataki left office, Bruno has been New York's top Republican leader.
"Frankly, my work is fairly well done," Bruno said Tuesday at his last major public event, an announcement of an IBM Corp.
high-technology project in Albany. "I feel like my transition is done. The furniture is moving out of my office tomorrow, the pictures are off the walls."
Then Bruno, true to form, joked: "It can get depressing if I hang around. I push the buttons and nobody's answering."
His term would have ended Dec. 31. A general election in November will pick Bruno's successor, who will be sworn in in January.
He said his exit doesn't threaten the Republicans' majority, now that the regular session is over. The Senate's Republican majority would likely only convene a special session if there was broad agreement on issues with the Democratic minority.
With Bruno's departure, and Democratic Sen. John Sabini taking over as head of the state's Racing and Wagering Board, Republicans will maintain a 31-29 advantage in the chamber they have controlled since the 1960s.
Bruno leaves behind numerous projects in his home district named for him - such as Joseph L. Bruno Stadium - or which honor him with statues or plaques, such as the bust of him in Albany International Airport. Bruno steered state and federal funding to numerous projects in his district as well as millions of dollars in pork-barrel spending for local groups, projects and charities.
He has also been part of Albany's notorious three-men-in-a-room negotiations with governors and the Assembly speaker to agree on state budgets and major policy matters behind closed doors.
"Upstate has never had a more dedicated advocate than they have had in Sen. Bruno," said Assembly Speaker Sheldon Silver, a Manhattan Democrat.
Bruno said he's had eight or nine opportunities presented to him in the private sector since his surprise announcement that he would relinquish the majority leader's job. He didn't identify any and said he's still thinking about how to return to the business world.
He ran a telephone company before being elected to the Legislature.
"I'm not the kind of guy who is going to go off and play with horses and golf or whatever else is out there," said Bruno, who owns horses and still rides.
He again told reporters that his decision has nothing to with a two-year-old investigation by the FBI into his consulting and other business ties outside the Senate.
"I am not worried about that," Bruno said, noting that he met with his lawyers Monday. "I have never been charged. There is nothing I could ever contemplate that was inappropriate or illegal."
