Byrne began his career with Sunderland. He signed for Scunthorpe United on loan in 2002.[1][2] After a successful three-month loan spell concluded in February 2003, Scunthorpe manager Brian Laws described Byrne as his best ever loan signing, attempting to sign him on a permanent transfer for £50,000.[3][4] Byrne initially turned down the move in order to fight for his place at Sunderland, but subsequently joined Scunthorpe after being released by Sunderland in the summer.[5][6][4]
Following the departure of Izzy Iriekpen[7] Byrne was given the captaincy of the side. He scored two goals in the last two games of the 2008–09 season; his 89th-minute goal against Tranmere Rovers was enough to help Scunthorpe seal the last playoff place.[8] After missing just under a year of action due to injury, Byrne made his first start of the 2011–12 season on 26 November 2011, away to Notts County. He was released by the club in May 2012.[9]
On 27 July 2012, it was announced that Byrne had signed for Oldham Athletic.[10] Byrne scored his first goal for Oldham against his old club Scunthorpe United in a 2–2 draw on 1 January 2013[11] He rejoined former club Scunthorpe on loan in September 2013. On 17 January 2014, Cliff had his contract at Oldham Athletic cancelled by mutual agreement.[12]
On 21 June 2019, he was appointed assistant manager again to Grant McCann, following his appointment as head coach at Hull City.[19] Following the takeover of Hull City by Acun Medya, backed by Acun Ilıcalı on 19 January 2022,[20] McCann and Byrne were sacked a few days later.[21]
In February 2022, Byrne became assistant manager at Peterborough United, once again assisting McCann.[22] The duo were sacked in January 2023.[23]
In May 2023, Byrne was reappointed as assistant manager to McCann at Doncaster Rovers.[24][25]
