Benali was waved off by friend and former team-mate Alan Shearer as he embarked on the 1,000 mile marathon journey from Newcastle United's St James' Park stadium.
A fearless left back in his prime, Benali will be running around 40 to 50 miles a day for 21 consecutive days as he aims to raise £1million for Cancer Research UK.
The challenge, which has been labelled Benali's Big Run, will see the 45-year-old run to all 20 grounds across a three week period - seeing him finish at St Mary's on September 13 as Saints play the Magpies in the league.
He is heading towards Sunderland's the Stadium of Light before the route takes him to Hull, Burnley, and both Liverpool clubs.
Benali raised more than £31,000 for the charity before even taking one stride forward in the challenge.
Talking to the Daily Echo before his run, Benali said: “I'm definitely feeling a lot fitter than I ever have.
“I'm really excited to get going. There's been so much organisation. A lot of work has gone in and now I just can't wait to get going.
“But my body feels ready and I feel confident that I've put the work in that will see me get through the challenge ahead.”