Reed was born in Chambersburg, Pennsylvania. After moving to Harrisburg in the 1950s, Reed attended Bishop McDevitt High School, where he graduated in 1967. He went on to attend Dickinson College and was named a Finnegan Fellow in 1970. He did not graduate from Dickinson and later served as an emergency medical technician in Harrisburg, while pursuing his early political career.
Active in the Democratic Party as a teenager, Reed headed the Teenage Democrats of Pennsylvania, was Vice-President of the College Young Democrats of Pennsylvania, and was active in many civic activities. Among his early work experiences was a staff job for the Democratic Caucus in the Pennsylvania House of Representatives.
In the Democratic landslide victory year of 1974, when he was 25, Reed campaigned hard for the Pennsylvania House of Representatives, and upset four-term Republican incumbent George Gekas, who later became a Pennsylvania state senator and U.S. Congressman. He would go on to serve three terms as a member of the state’s House of Representatives until 1980.
Re-elected to the state house in 1976 and 1978, Reed was elected Dauphin County, Pennsylvania Commissioner in 1979 and Mayor of Harrisburg in 1981. He has won re-election as mayor in 1985, 1989, 1993, 1997, 2001 and 2005. During the 2000s, he was considered "Pennsylvania's most popular and successful mayor."
During Reed's tenure, restaurants, museums, hotels, several large office buildings and new residences were constructed within the city limits. Reed was instrumental in the city getting its minor league baseball team, the Harrisburg Senators, and later led the city to purchase the team when it was sold to a buyer who intended to move it out of the region.