Leverkusen, who face Feyenoord in the Champions League next week, struck twice in the first half-hour for a 2-0 lead with Boniface setting up Martin Terrier for a tap-in in the 17th minute and the Nigerian turning scorer in the 30th.
Hoffenheim's Mergim Berisha, making his first appearances since a knee ligament tear last November, cut the deficit in the 37th but Leverkusen restored their two-goal lead courtesy of a Florian Wirtz penalty in the 72nd.
Boniface then single-handedly dismantled the Hoffenheim defence with a strong run down the left, powering a short past keeper Oliver Baumann in the 75th to lift Leverkusen to fourth place on six points.
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