Dani Olmo scored both goals early on as Julian Nagelsmann's side recorded a third successive triumph on the road since the 2019-2020 season resumed in Germany.
The Spain international grabbed the opener in the ninth minute, finishing off a flowing move as he slotted a low shot beyond Hoffenheim goalkeeper Oliver Baumann.
A second soon followed for the January recruit, Olmo applying a first-time finish after the ball was headed into his path by team-mate Marcel Sabitzer.
Timo Werner missed the chance to increase the lead just before the break, the striker, who is widely expected to join Chelsea in the next transfer window, shooting over when in the clear.
Christopher Nkunku hit the post in added time for Leipzig, which now sits just a point behind second-placed Borussia Dortmund as it aims to qualify for next season's UEFA Champions League.