The young Reds will host Leeds United in the U18s Premier League North at the club's iconic former training ground.
The decision to make use of the venue for Marc Bridge-Wilkinson's side was taken due to the U23s and U16s also being in action on a busy day at the Kirkby Academy.
Bridge-Wilkinson expects the 12pm GMT kick-off to be an unforgettable occasion for his players.
"It's an absolute honour for us to get this wonderful opportunity to play at Melwood," he told Liverpoolfc.com.
"I can tell you the lads and staff all can't wait to play there on Saturday.
"Melwood is such an iconic place in Liverpool's history and it really is special for the Academy to get this opportunity."
The match at Melwood will be played behind closed doors, in line with COVID-19 restrictions. Highlights will be available on Liverpoolfc.com on Monday.