Nkunku began to carve Schalke open in the second half, drawing a smart stop from home keeper Alexander Nübel and giving Sabitzer a golden opportunity to complete his brace, only for the Austria international to drag wide.
Undeterred, the former Paris Saint-Germain man slipped through to Timo Werner on the hour mark, and the Germany star took care of the rest, blasting high past Nübel for 2-0.
A few minutes later the contest was all but settled as Nkunku whipped in a corner which Marcel Halstenberg headed home from close range.
With around 10 minutes to go, Nkunku cantered down the left flank and squared for Angelino, who did brilliantly to skip past Jonjoe Kenny and drill home his first goal for Leipzig since joining on loan from Manchester City in January.
No.18 then rounded out a masterful performance by sneaking a pass between two defenders for Emil Forsberg, who slammed in to complete the 5-0 rout.
It's been over seven years since a player assisted four goals in a single Bundesliga outing. The last man to achieve the feat was former Hungary midfielder Szabolcs Huszti, who set up all four of Hannover's goals in a 4-0 win over Wolfsburg in September 2012.