The world champion controlled the match throughout, averaging 91.86 and completing the win with a stunning 170 checkout to clinch the final set.
De Decker won only two legs and struggled to find rhythm on his doubles, while Littler's consistency on scoring visits and composure on finishes ensured there was little jeopardy across the contest.
The 18-year-old told Sky Sports after his win that he could feel a nine-darter coming.
"I said to myself, 'let's leave with a big one'.
"Mike didn't play his best, so I had to jump on it and lead early.
"This tournament is brutal. We have seen some shocks, but I had to do my job.
"I am hitting the double 20 and as a player you can feel that nine-darter coming..."
Gerwyn Price rounded off the evening's action with a 3-0 victory over Josh Rock, a result that sets up a mouth-watering quarter-final clash with Littler.
Price's performance was patchy but effective, highlighted by an 11-dart leg that included back-to-back 180s to break the Rock throw.
Rock's average drifted in the low 70s as missed opportunities on tops and double 20 proved costly, while Price's composure on key checkouts and 92.46 average eventually saw him through comfortably.
Clayton and Van Duijvenbode through
Earlier in the evening, Dirk van Duijvenbode cruised past Daryl Gurney 3-0 to book his place in the last eight.
The Dutchman raced through the opening two sets without reply and capped the performance with a superb 158 checkout to end the match.
His power scoring and consistent accuracy on double 18 proved too strong for Gurney, who struggled to find any rhythm.
Jonny Clayton also advanced with a 3-1 win over Luke Woodhouse in a scrappy encounter.
World number six Clayton averaged 85.67 and relied on steadier finishing to edge through, closing the match on his preferred double 16 after both players had endured lengthy spells of missed doubles.
The quarter-final line-up is now confirmed. Gerwyn Price will meet Luke Littler, Jonny Clayton faces Dirk van Duijvenbode, Luke Humphries plays Cameron Menzies, and Gary Anderson takes on Danny Noppert.
The quarter-finals take place on Friday evening, with Littler's meeting with Price set to headline the session.