The American was fastest in both legs to beat Croatia's Zrinka Ljutic by 1.24 seconds, with Switzerland's Michelle Gisin third.
The title lifts her level with compatriot Lindsey Vonn and Swedish great Ingemar Stenmark for the most in a single discipline.
Shiffrin had been absent since injuring her knee in a downhill at Cortina d'Ampezzo in Italy last January, losing her overall World Cup lead.
The slalom is her signature discipline, however, and she showed she was back with a bang by completing the first run in 49.94 seconds.
She then completed the second run in 53.01, 0.40 faster than home favourite Anna Swenn Larsson.
With only one slalom remaining at the World Cup finals in Saalbach-Hinterglemm, Austria, Shiffrin has an insurmountable 225 point lead over Slovakia's Petra Vlhova, who suffered a season-ending injury in January.
The American is third in the overall standings, 345 points behind Switzerland's Lara Gut-Behrami, but has said she will not compete in the super-G and downhill events at the March 16-24 finals.
"It was so nice to race again today, and some nerves and all the emotions that I hoped to feel," said Shiffrin, who celebrates her 29th birthday on Wednesday.
"Really proud of my whole team and for sure proud of myself to get back here...the second run was some of my best skiing so I'm just so happy to be able to do that again this season.
"First run I felt actually like I was pushing really hard but sometimes I wasn't keeping up with the pace of the course," she added. "This (second) run was, like, I wouldn't change one thing."
Shiffrin took her first ever World Cup win in Are in 2012 and also a record-breaking 87th there last March.
