A Frankfurt side without a league clean sheet in 12 matches saw their wait for a shutout extend after just 45 seconds here, as Ezechiel Banzuzi turned home at the back post from point-blank range after a Neal El Aynaoui cross had been allowed to drift across the box.
Just four minutes later, Die Roten Bullen doubled their lead thanks largely to the endeavour of Antonio Nusa, who outmuscled his marker down the left before squaring for Nkunku to sweep into the far corner.
The shell-shocked visitors stemmed the bleeding from there and enjoyed arguably the better of much of the first half, but their failure to create clear-cut chances undermined their efforts.
Ritsu Doan and Ansgar Knauff were both denied by Marten Vandervoordt, whose interventions looked pivotal when a late flurry before the break saw Leipzig go into half-time with a four-goal lead.
Nkunku’s 50th goal in the Bundesliga came on the rebound after Romulo Cardoso’s audacious flick had been kept out by Frankfurt stopper Noah Atubolu, who was culpable for the Frenchman’s next strike.
Banzuzi’s low drive was haplessly parried into Nkunku’s path by Atubolu, and the Leipzig forward made no mistake to complete his first Bundesliga hat-trick.
Damage limitation was Frankfurt’s primary objective after the break, but their resistance was broken within nine minutes of the restart by the electric Nusa, who drove at the heart of Die Adler’s defence and fired into the near bottom corner.
The visitors received a welcome reprieve just beyond the hour when Castello Lukeba blazed over from a few yards out when it seemed easier to score, but Adi Hutter’s men still conceded again late on as Tidiam Gomis drove through the centre of the pitch and picked out the far corner.
Just a second defeat from seven away games leaves Frankfurt languishing in the bottom half of the table having conceded a whopping 15 goals from their five league outings. Leipzig, meanwhile, climb into the top five thanks to a seventh head-to-head victory in 11 home meetings with Frankfurt in the Bundesliga.
Flashscore Man of the Match: Christopher Nkunku (RB Leipzig)