Safran's first experience of national fame came via Race Around the World, a television competition for young documentarians run by the ABC. Safran's segments scored well with both the judges and the public audience, Safran topped the viewer poll. He was, however, disqualified for a segment taped in a confessional booth (the program forbade hidden camera footage), the disqualification of the segment and subsequent loss of points meant that he finished last in the first season.
Safran went on to create television shows such as John Safran's Music Jamboree, John Safran vs. God, Speaking in Tongues and John Safran's Race Relations. Since 2007, Safran has hosted Sunday Night Safran on triple j with Father Bob Maguire. In 2013, he published his first book, Murder in Mississippi.
To date, Safran has appeared on The Little Dum Dum Club three times. His first episode was in 2011, the show's 30th episode overall. A standalone guest, the episode was later picked up by triple j for some controversial comments about comedian Lawrence Leung. He returned for a live episode alongside Anyone for Tennis?, Luke McGregor and American comedian Kumail Nanjiani. His most recent appearance came in 2013 for the show's 159th episode alongside Ronny Chieng.