The 2014 Olympic champion, who led after the first run in Courchevel, finished 0.29sec ahead of Slovakia's Petra Vlhova and 0.37sec ahead of Sweden's Frida Hansdotter in third place.
It capped an impressive 24 hours after she had won the giant slalom in blizzard-like conditions on Friday.
Despite her achievement Shiffrin said she was not driven by setting records after becoming the first woman to secure a half century of race victories before her 24th birthday, which she will celebrate in March.
"It's not really my motivation to break records, my big motivation is to ski very well," she said.
"Today everybody was asking about 50 and I was really trying to focus just on skiing, making the best turns that I could," she added.
Racing men is not one of my goals: Shiffrin
Shiffrin praised the efforts of others in achieving the landmark.
"If you asked me 10 or five years ago I would never think I would be in this position. It's a lot of hard work from my team, my coaches, for me, I have a lot of support and I'm really grateful for that. That brought me to this place with 50 victories," Shiffrin said.
Hansdotter predicts further success for Shiffrin. "She can beat all the records possible. To have won everything she has won at 23 is so impressive," she said.
Shiffrin won Friday's giant slalom by overcoming a 0.08sec deficit and the severe conditions. Victory on Saturday was her fourth consecutive win in the French resort.
Sweden's Ingemar Stenmark holds the record for both men and women with 86 career successes.
Shiffrin's fellow US racer Lindsey Vonn has the most female wins with 82 victories across all five alpine disciplines. Vonn is expected to return to the circuit early in 2019 after recovering from injury.
At the age that Shiffrin is now, Vonn had only triumphed on 13 occasions and Stenmark 44.
The Colorado native joins retired Austrian Marlies Schild with a record 35 slalom World Cup titles.
Shiffrin leads the overall standings on 889 points after 13 out of the 38 events, twice as many as the combined points of both Vlhova in second place and Norway's Ragnhild Mowinckel in third.
She can continue her already illustrious career by adding a fourth World Championship title to her name in Are, Sweden in February.
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