Durant eclipsed 40 points for the third time in four games, and he leads the NBA with five 40-point games this season.
The league's scoring leader hit two free throws, a jumper and a 3-pointer from the right wing, and then a driving foul-line jumper during a 10-2 run that put the Thunder in control midway through the fourth quarter.
David West had 20 points and 15 rebounds and Chris Paul scored 15 points for New Orleans, which has lost three of four following a 10-game winning streak.
The win put Oklahoma City a half-game ahead of the Hornets for fourth place in the Western Conference and clinched the season series for the Thunder.
The Hornets pulled out a 91-89 win against Oklahoma City just nine days earlier in New Orleans, with Paul coming up with a steal in the final 15 seconds that led to West's winning basket.
This time, Durant ensured there would be no late-game meltdown by the Thunder.
His hot stretch extended Oklahoma City's six-point lead to 98-84 with 5:44 to play, and the Hornets couldn't mount a comeback. Durant scored 47 points at Minnesota and then 40 against Washington in back-to-back victories last week that both went past regulation, and he shot 14 for 19 from the field in his latest scoring outburst.
Jeff Green added 12 points and Serge Ibaka had eight points, 12 rebounds and six blocks as the Thunder bounced back from a loss to Miami on Sunday. Oklahoma City hasn't lost back-to-back home games since December 2009.
New Orleans' David Andersen scored a season-high 13 points while helping to fill in for the injured Emeka Okafor (left oblique strain). The Hornets also lost Trevor Ariza to a sprained right ankle in the third quarter, when Oklahoma City turned the game around by outscoring New Orleans 32-17.
Durant capped a personal 6-0 run by connecting on a fallaway jumper along the right baseline with 0.2 seconds left in the third quarter to put the Thunder up 81-72.
Daequan Cook stretched the lead to 12 by opening the fourth with a 3-pointer from the right wing after Nick Collison had saved the ball in the opposite corner of the court.
Willie Green and Andersen hit 3-pointers on back-to-back trips to get the Hornets within six, and the Hornets were back within 88-82 after Quincy Pondexter's jumper on the left baseline before Durant put it away.
The Thunder had a string of sellouts snapped but still drew 17,849 fans while crews were using construction equipment and dump trucks to clean snow off downtown streets after a rare blizzard dropped a foot of snow in some areas around the city.
Paul was carried off the floor by two trainers, then limped to the locker room after rolling his left ankle on the top of Ibaka's right shoe as he drove to the basket midway through the first quarter.
The Hornets scored on just one of their next five possessions as Oklahoma City put together an 11-2 run and went up 25-18 after Collison's jumper in the lane.
Andersen scored 10 of New Orleans' first 14 points of the second quarter to lead a comeback, and his jumper put the Hornets back on top 39-38 just before Paul returned to the lineup. Andersen hadn't scored more than nine points in a game all season, then did it in a 6-minute span against Oklahoma City.
Paul's 3-pointer from the right wing started a 7-0 run by the Hornets, and New Orleans led 55-47 before Durant closed the first half with a jumper from the top of the key for the Thunder.
NOTES: Thunder G Thabo Sefolosha missed his third straight game with a left knee sprain and C Nenad Krstic suffered a right foot sprain in the third quarter. ... New Orleans' team bus got caught in the snow after making it to Oklahoma City early Wednesday, and Ariza and Paul both hit coach Monty Williams with snowballs while the bus was being freed. "It was a tough situation but I thought we turned it into a fun one," Williams said.