The German club continued their perfect start to the group stage with a win over the Czechs.
Three players scored in the first 21 minutes of the game to make it easy for the champion to win.
Sane made it four in the second half.
The win gives them nine points from their first two games.
The preparations for this game were disrupted when Joshua Kimmich and Thomas Muller were ruled out.
Sane scored a superb goal in the 7th minute.
Goretzka carried the ball through the middle of the field and laid it off to Gnabry who scored off the inside of the post.
There were no doubts about the outcome. It was his pace and anticipation that enabled him to run onto the loose ball and score the goal.
After Musiala had a goal ruled out for being in an ineligible position, it was soon four after the break when Sane ran onto a lofted through ball from Mane and hit it past the keeper.
Sane has four goals in three games in the group stage.
Goretzka's through ball found Choupo-Moting, who curled the ball in from 15 yards.
Hoffenheim's side are third in the league, behind Union Berlin and Freiburg.
They are living up to their billing as one of the tournament favorites, despite being in a difficult group that included Barcelona and Inter Milan.
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