Brown, who is serving his seventh term of office, was diagnosed with cancer in December and has been working from home during his treatment for the disease.
"I had hoped to return to office and complete my term, but my medical condition makes that impossible," Brown said in a statement.
"As much as I will miss this job, I look forward to my retirement, and the opportunity to spend more time with my family and friends," he said.
Brown, 66, was appointed to the District 2 seat in 1983 by his cousin, first-time Gov. Jerry Brown, to fill the seat vacated by Barbara Boxer when she was elected to the U.S. House of Representatives. Gov. Brown will appoint a successor to serve the rest of Hal
Brown's seat that ends Dec. 31. 2012.
"It has been a privilege to serve the people of District 2 and the county," Brown said. "They have demonstrated to me over and over again, all the best that people can be -- caring for each other, and about the community they live in."
Brown is known as a fiscal conservative who espouses the importance of setting aside budget reserves for lean times.
Board of Supervisors Chairwoman Susan Adams said Brown is "a legendary Marin County Supervisor."
"He has dedicated his life to effectively serving the residents with his own unique, no-nonsense style. His humor and knowledge will be greatly missed by our Board and his constituents. We wish him the best," Adams said.
Brown championed open space and the acquisition and preservation of 1,700 acres in Ross Valley.
He spearheaded the county's original pest management policy in 1983 and founded FireSafe Marin in 1992.
He galvanized support for flood control in Ross Valley, paving the way for the adoption of the Ross Valley Watershed and Flood Protection program.
He also was on the Golden Gate Bridge District's Board of Directors for 20 years and is the senior member of the Bay Area Air Quality Management's Board of Directors.
The Board of Supervisors will acknowledge his service at its Oct. 18 meeting, and a charity event will be held later this year.