The Frenchman suffered the injury to his left knee against Crystal Palace in April - having recovered from the same injury to his other knee a few months earlier.
After undergoing surgery, he spent time at a rehabilitation centre in Rome before returning to Tyneside for pre-season, and has steadily built up the strength in his knee over the last few months.
Speaking in an interview with nufc.co.uk last month, the 28-year-old said: "I had great support from the whole of my family, the club and of course there were all the messages from the Newcastle fans which really touched me too."
Lejeune has now returned to full training and will play his first match since his operation as Neil Redfearn's under-23s take on their North East neighbours in Premier League 2.
Kick-off at Whitley Park is at 7pm (GMT) and admission is free to season ticket holders, otherwise it's £3 for adults and £1 concessions.