In 2008, Keeffe was signed by the Collingwood Football Club as an unregistered player and was later drafted with pick number 69 in the 2009 Rookie Draft. He has previously played for Old Trinity in the VAFA.
In 2011, Keeffe played in Collingwood's NAB Cup pre-season campaign, including the winning Pre Season Grand Final win against Essendon. Keeffe made his senior AFL debut against North Melbourne in round 16, 2011 at the MCG.
Keeffe, along with teammate Josh Thomas, tested positive to the banned substance clenbuterol in drug tests taken in February 2015. Both players accepted provisional suspensions in March 2015. On 10 August 2015, Thomas accepted his two-year ban from the tribunal and that day was delisted by Collingwood football club but was told he'd be re-drafted as a rookie for the 2017 season if still available in the draft. He was banned from AFL competition until 9 February 2017
On 27 November 2015, Keefe and his teammate Josh Thomas were re-drafted to Collingwood through the rookie draft.