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Jenkins, who finished with 28 points, also had the tying 3-pointer with 2.7 seconds left in regulation as Hofstra clinched a top-four finish in the Colonial Athletic Association and a bye in the opening round of the conference tournament.
Mike Moore added 25 points as the Pride (18-9, 12-4) earned its fourth consecutive victory and overcame a double-digit deficit for the seventh time this season.
Quinn McDowell, who led William & Mary (7-20, 3-13) with 28 points and 12 rebounds, hit two free throws with 4.5 seconds left in overtime, tying the score at 78.
Jenkins, whose 3-pointer at the end of regulation tied the score at 69, answered McDowell's free throws by hitting the winning 3-pointer over two defenders.