She finished second to Tina Maze, of Slovenia, in the season's third and final super-combined, a result that was enough to clinch the championship for the discipline.
"It's been a tough season for me in slalom and I was trying really hard today," Vonn said. "Every title means a lot to me. ... I knew I had to risk everything if I wanted to win the title. I just tried to go straight at the gates and I was really happy with my run."
Vonn still trails German rival Maria Riesch by 176 points in the overall standings. The U.S. star missed the second half of February's world championships because of recurring symptoms from a mild concussion.
Vonn finished with 220 points in the super-combined standings. Maze's win lifted her to second at 212. Riesch, the leader coming into the race, dropped to third at 205.
"I got some good points today," Riesch said. "It wasn't enough for the globe, which is a little bit sad, but I didn't have a great slalom run and Lindsey deserved it today."
This was the 10th World Cup title of Vonn's career, following three overall crowns, three downhill titles, two in super-G and last season's super-combined victory. Vonn also has a chance to clinch this season's downhill and super-G titles in races today and Sunday.
Maze, fifth after the downhill leg, produced a blistering slalom for a combined time of 2 minutes, 13.54 seconds. Vonn was 0.18 behind and Riesch was 0.55 back in third.
Maze was a popular winner, with the Slovenia border only about a 10-minute drive away.
"I've been saying that Tarvisio was like my home race this season since Maribor was canceled," said Maze, who took silver in super-combi at worlds. "A lot of fans came across the border today, and even my dog, Mik, came to watch me for the first time -- and he brought me gold."