Born in Shankill, Dublin, Cuffe went to school at the Children's House Montessori School in Stillorgan, Gonzaga College in Ranelagh, University of Maine at Orono, USA, University College Dublin, and the University of Venice, Italy. He joined the Green Party in 1982, and campaigned with Students Against the Destruction of Dublin in the 1980's. He has degrees in architecture, and town planning from University College Dublin. Cuffe was twice elected to Dublin City Council in 1991 and 1999.
He lectured in urban planning at the Dublin Institute of Technology, Bolton Street prior to his election to Dáil Éireann in the 2002 general election. He was re-elected in the 2007 general election, beating the People Before Profit Alliance's Richard Boyd Barrett by 9910 votes to 7890 votes in the 10th Count.
Just after the election on 28 May 2007, he wrote on his blog: "A deal with Fianna Fáil would be a deal with the devil. We would be spat out after 5 years, and decimated as a Party".