Griffin is a former member of Kerry County Council, representing the Dingle area from 2009 to 2011. He was the subject of controversy for hiring his wife Róisín as his secretarial assistant and his cousin Tommy Griffin as his parliamentary assistant. Both these positions were filled without interview and have salaries paid for by the state. In addition, Griffin helped another cousin, Matt Griffin, get his old council seat. He takes half of his TD salary, at first giving the other half directly back to the exchequer and then in 2012 donating the other half of his salary to pay for a third teacher, in a small rural Kerry school.
In 2011, Griffin was chosen as Fine Gael's second candidate in Kerry South, while Tom Sheahan was an incumbent TD. Despite unpromising opinion polls, Brendan Griffin topped the pole with 8,808 first preferences votes, over three thousand more than his colleague who poled 5,674. He was deemed elected to Dáil Éireann, after Count 5, soon followed by Tom Fleming and Michael Healy-Rae.
In The Tallyman's Campaign Handbook for 2016, author Noel Whelan stated that in the new 5 seater constituency, incumbent TDs Tom Fleming and Brendan Griffin would battle it out for the final seat, while Michael Healy-Rae, Jimmy Deenihan and Martin Ferris would be comfortably returned, as well as Fianna Fáil candidate John Brassil. Tom Fleming later announced in February that he would not contest the upcoming general election, while Danny Healy-Rae added his name to the ticket, forming a vote strategy with his brother Michael.
Fine Gael had a very disappointing general election nationally, but Brendan Griffin improved his first-preference vote to 9,674, polling third. This was the highest vote achieved by any Fine Gael candidate in Munster, as well as being the largest vote a Young Fine Gael candidate secured in Ireland. He was returned to Dáil Éireann, on Count 11, after both his government colleagues Jimmy Deenihan and Labour's Arthur Spring were eliminated.
On 11 July 2016, Brendan Griffin did an interview with RTÉ Six One News calling for Taoiseach Enda Kenny to step down as Leader of Fine Gael, before the Dáil returned in September. Griffin was not backed by a single TD and a vote of confidence was not held. Griffin argued that Fine Gael showed a lack of preparedness for an election in the scenario where it arose.