With the game still poised at 0-0, Nelson picked up a short corner and made his way to goal.
Goalkeeper Lukas Hrdecky then had no answer to a wonderful curled effort from wide, which made its way into the top corner.
Nelson's strike opened the floodgates, as further goals from Vincenzo Grifo and a double from Joelinton sealed a 4-1 victory on the road for Hoffenheim.
The teenager now has five goals in the Bundesliga, with the promise of plenty more as he continues to take Germany by storm.
He is also the third-youngest player to reach the mark in the league, after Lukas Podolski and Olaf Thon.