The Japan international put die Nullfunfer ahead in the 75th minute when he headed home Maxim Choupo-Moting's cross to make it three goals in eight minutes from the visitors.
Okazaki was then on hand to give Mainz a two-goal victory with the final touch of the game in injury-time as Thomas Tuchel's side complete a resounding second-half comeback.
Okazaki's double proved the difference in the end as the Karnevalsverein went fifth on the German table while Hoffenheim remained tenth.
Okazaki was delighted to be a major part of his side's victory as they get set for runaway league leaders Bayern Munich next weekend.
"I was just thinking about scoring today so it was great to be able to do that," said Okazaki who has now scored 11 league goals since his summer move from Stuttgart.
"At the end of the day, I'm judged on how many goals I score.
"But we've got Bayern next. I'm not sure how, but we've managed to be in fifth place so hopefully we can build on this. Against Bayern, you concede one and it's over so we've got to do much better than we did today."
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