Kenin, still just 20, took the first set 6-2 before winning the second 7-5 to complete a remarkable achievement.
This defeat will raise questions about Williams' ability to continue to compete at the top end of women's tennis.
Kenin's ability to attack Williams' serve proved key during the opening set. She frequently put the veteran on the edge of being broken:
Eventually, Kenin earned a pair of breaks, which allowed her to take the set. Aside from her ability to wreck the Williams serve, Kenin was also causing havoc with a series of deft drop shots that challenged the 37-year-old's ability to move swiftly across the red clay in Paris.
It seemed Kenin had her decorated opponent well scouted. Ben Rothenberg of the New York Times offered one reason why the younger player may have had the inside track to victory:
Kenin also wasn't above gaining a psychological edge to keep Williams rattled:
The effect was obvious as Williams continued to struggle finding her range. Too many shots were rushed and missed as Kenin kept the pressure on.
Said pressure yielded another valuable break for Kenin early in the second set.
It took a defiant show of resilience for Williams to put a halt to an alarming run of losing:
Williams sensed a telling moment and soon forged her way into a 4-3 lead. However, the pace of the Kenin serve was still causing her problems, and the set was even in no time.
Both players held serve before Williams missed a key forehand to put another break in sight for Kenin. A double-fault pushed Williams closer to a failure to hold, and Kenin broke decisively with a stunning forehand to leave her serving the set.
Despite some mistakes, Kenin eventually held her nerve to condemn Williams to an early exit on a day when self-inflicted mistakes ultimately undid the 23-time Grand Slam winner.