Media playback is not supported on this device
Italy threatened a shock in an error-strewn first half that saw Dan Jones and Matteo Minozzi land two penalties apiece.
But Wales got on top with tries from Harrison Keddie (2), Shaun Evans and Joe Thomas.
Jones took his points tally to 15 at a packed Parc Eirias.
Wales' closest match during the campaign was their 18-15 victory over Scotland in round two, when a 79th-minute penalty by replacement Billy McBryde capped a Welsh comeback.
They now face Ireland, Georgia and New Zealand in the Junior World Championship in Manchester in June.
Wales have previously taken the Under-21s Six Nations title in 2005, captained by James Merriman, and 2003, led by current Wales squad prop Paul James.
Ex-Wales fly-half Stephen Jones, now Scarlets backs coach, led Wales U21s' Five Nations triumph in 1999.
Wales Under-20s: Rhun Williams (RGC); Joe Thomas (Ospreys), Harri Millard (Cardiff Blues), Owen Watkin (Ospreys), Keelan Giles (Ospreys); Daniel Jones (Scarlets), Reuben Morgan-Williams (Ospreys); Corey Domachowski (Cardiff Blues), Dafydd Hughes (Scarlets), Dillon Lewis (Cardiff Blues), Shane Lewis-Hughes (Cardiff Blues), Adam Beard (Ospreys), Tom Phillips (captain, Scarlets), Shaun Evans (Scarlets), Harrison Keddie (Newport Gwent Dragons).
Replacements: Ifan Phillips (Scarlets), Rhys Fawcett (Scarlets), Leon Brown (Newport Gwent Dragons), Bryce Morgan (Newport Gwent Dragons), Morgan Sieniawski (Cardiff Blues), Declan Smith (Scarlets), Billy McBryde (Scarlets), Joe Gage (Ospreys).
Italy Under-20s: Luca Sperandio; Pierre Bruno; Roberto dal Zilio, Lorenzo Masato; Matteo Minozzi; Charly Trussardi; Daniele Rimpelli; Marco Manfredi, Marco Riccioni (capt), Leonard Krumov, Samuele Ortis, Lorenzo Masselli, Davide Ciotoli, Giovanni Pettinelli.
Replacements: Nicola Broglia, Damiano Borean, Giosue Zilocchi, Vittorio Mantegazza, Michael de Marco, Giovanni Lucchin, Marcello Angelini, Leonardo Mantelli.
Referee: Frank Murphy (Ireland)
Assistants: Kieran Barry, Brian MacNeice (both Ireland)
TMO: Kevin Beggs (all Ireland)
Wales earned their first ever Six Nations Under-20 title and Grand Slam with a dominant second-half against Italy at Colwyn Bay.