There were five different goalscorers for the young Reds at the club's iconic former training ground as they raced into a 3-0 lead in the first half.
Mateusz Musialowski netted his first goal for the club to open the scoring and was joined on the scoresheet by Layton Stewart, Melkamu Frauendorf and substitutes Isaac Mabaya and Oakley Cannonier.
Goalkeeper Marcelo Pitaluga also made his competitive debut for Liverpool and produced a number of smart interventions to secure a clean sheet.
Speaking to Liverpoolfc.com post-match, U18s boss Marc Bridge-Wilkinson said: “I thought we played well. We set out to come here and win the game, like we do every week.
“We wanted to perform and, because of where we were playing, it was something that we wanted to do properly. We wanted to leave Melwood in the way that we could – by being a really good Liverpool side.
“Our job as maybe the last Liverpool team to play here was to make sure we won the game and to make sure we did it in a way that was befitting of the club and the badge. Hopefully we did that.”
LFCTV GO: Watch the best of the 5-0 win
Bridge-Wilkinson's side started as they meant to go on in West Derby and took a deserved lead in the 15th minute.
Musialowski picked up possession inside Leeds' half and went on a weaving run before applying a powerful finish that found the top corner.
The home side doubled their advantage in minute 35 when Stewart slid in to convert James Norris' cross into the box after a charging run from the left-sided full-back.
In the closing moments of the opening half, Stewart turned provider when he delivered a cut-back that found the well-timed run of Frauendorf, who thrashed a strike beyond the goalkeeper.
U18s captain Jarell Quansah was unable to return following the half-time break and replaced by Mabaya, who required just five minutes to make an impression on the game.
As Dominic Corness' corner was half-cleared by Leeds, Mabaya's drilled shot in the aftermath took a slight deflection on its way to the bottom corner.
Liverpool's dominance continued and they had plenty of opportunities to make it 5-0. They finally capitalised on one with two minutes left to play when Stewart's cross from the left evaded Leeds' backline, allowing Cannonier to smash a finish into the net.
Liverpool U18s: Pitaluga, Wilson, Quansah (Mabaya, 46), Miles, Norris, Corness, Frauendorf, Balagizi, Woltman (McConnell, 88), Musialowski (Cannonier, 67), Stewart.
Unused substitute: Davies.