The projected lottery pick scored 19 points in the second half, where the unranked Wildcats (16-5) produced a memorable comeback.
After James Bolden's transition 3 tied the game at 74-all, Knox delivered the counterpunch, a go-ahead 3 from the wing with 1:10 left.
Jevon Carter's 26 points and seven assists weren't enough to save West Virginia (16-5) from another collapse in its home arena. Two weeks ago, the Mountaineers blew a 16-point lead to Kansas.
Bolden finished with 17 points on 5-of-10 shooting from 3-point range, a much-awaited performance by the Covington, Ky., native against the home-state Wildcats he grew up adoring.
Sagaba Konate had 13 points and seven blocks for the Mountaineers, but missed a one-and-one with 46 seconds left before Nick Richards' putback dunk gave the Wildcats a 79-74 cushion.
Jarred Vanderbilt grabbed 11 boards and Richards had eight to fuel Kentucky's 49-34 rebounding edge. That included a 29-13 margin after halftime.
Knox's previous season-high was 25 points against UIC in November. The stakes and the stage were considerably larger this time.
He made 11 of 17 shots overall and 5 of 8 from 3, as his team won for the second time since falling out of the AP Top 25.
Making its first visit to Morgantown in 47 seasons, Kentucky struggled with turnovers and trailed 50-33 early in the second half.
As a freshman, Carter was part of a 78-39 blowout loss to the Wildcats in the Sweet 16. In the rematch, he made sure WVU surpassed that offensive output in the first half, making all four 3-pointers and scoring 20 points when the lead stood 48-33.
But Kentucky's freshman-driven lineup reeled off 50 points after halftime, making 18 of 18 free throws.
Hamidou Diallo added 13 points for the Wildcats. They committed 16 turnovers, two more than their season average, but only five occurred after halftime.
Forward Esa Ahmad, expected to give the Mountaineers a midseason boost after returning from an NCAA suspension, shot 0-of-7 from the floor and went scoreless for the second straight game.
--Field Level Media
Kentucky | West Virginia | |
Kevin Knox 34 | Scoring | Jevon Carter 26 |
Shai Gilgeous-Alexander 5 | Assists | Jevon Carter 7 |
Jarred Vanderbilt 11 | Rebounds | Sagaba Konate 6 |
Kevin Knox 7 | Free Throws Made | Jevon Carter 4 |
Quade Green 1 | Steals | Jevon Carter 2 |
Wenyen Gabriel 3 | Blocks | Sagaba Konate 7 |
Team | Points | FG% | 3PM-3PA | FTM-FTA | Assists | Rebounds | Blocks | Steals | Turnovers |
Kentucky | 83 | 44.8 | 8-18 | 23-29 | 16 | 47 | 7 | 1 | 16 |
West Virginia | 76 | 39.7 | 10-24 | 12-18 | 12 | 30 | 7 | 6 | 6 |