O'Keeffe was born in Fermoy, County Cork, but the family moved to Tralee, County Kerry when he was nine-years-old. His first competitive football was played with a junior team, the Rangers, but when he advanced to senior grade he joined Kerins O'Rahilly's and with them won two County Championship titles. O'Keeffe made his first inter-county appearance on the Kerry junior team that won the All-Ireland Junior Championship in 1930. A year later he was substitute goalkeeper on the Kerry senior team to meet Kildare in the All-Ireland final, however, a few hours before the game he was informed that he would be playing and collected his first winners' medal. O'Keeffe was first-choice goalkeeper for seventeen years in total and claimed a then record of seven All-Ireland Championship titles. His other honours include a record 14 Munster Championship medals and two National League titles. O'Keeffe was also a regular on the Munster team and won three Railway Cup medals, including one as captain of the team. Playing until he was 41 years old, he was posthumously named on the Football Team of the Century and the Football Team of the Millennium.
