The former Netherlands international was confirmed as former boss Gary Rowett's replacement on Thursday, just over four months after leaving his previous role in charge of Royal Antwerp.
Rowett departed the Pirelli Stadium last month to take over at Championship side Birmingham City, but Burton began life after their former coach with an impressive win at Adams Park.
Phil Edwards headed in from a Matthew Palmer cross as the game sprung into life in the 38th minute, before Matt Bloomfield fired wide at the other end.
Hasselbaink's men doubled their advantage four minutes into the second half when Alexander MacDonald slotted into the bottom right-hand corner, but Wycombe refused to go down without a fight.
Hogan Ephraim burst into the Burton penalty area in the 65th minute only to be stopped in his tracks by Shane Cansdell-Sherriff to earn a penalty, which Paul Hayes coolly converted.
Ephraim should have levelled a minute later, but lifted over the crossbar from the centre of the penalty area.
However, the points were in the bag for Burton when Jacob Blyth headed home in the 68th minute and Hayes had a goal chalked off for offside.
A head injury to Alfie Mawson led to a lengthy delay and 11 minutes of stoppage time at the end of the match, but Wycombe - who had used all of their permitted substitutes prior to Mawson's knock - were unable to claw their way back.
The result sees Burton climb to fourth, behind Wycombe on goal difference.
