The much-vaunted US stars were both looking to put some gloss on a mixed Games, with Shiffrin winning gold in the giant slalom but finishing fourth in her preferred slalom, and Vonn settling for bronze in the downhill.
Speed specialist Vonn was first after the downhill section of the combined and on course to add to her Olympic downhill title from 2010.
But the most successful female skier of all time missed a gate in the slalom, in all likelihood her final ever Olympic race.
Shiffrin went into the slalom in sixth place and skied into gold-medal position until Gisin bettered her combined time of 2:21.87 by 0.97 seconds.
The 24-year-old Gisin, third in the downhill and fourth in the slalom leg of the combined, followed in the footsteps of her sister, Dominique, who tied with Tina Maze for an unprecedented joint downhill gold in Sochi four years ago.
It was a successful day for the Swiss with Wendy Holdener, slalom silver medalist in Pyeongchang and reigning combined world champion, taking bronze.
Not to be for Vonn
Though slalom is not Vonn's strongest discipline, there was an outside chance she would add to her bronze after pipping double Pyeongchang silver medalist Ragnhild Mowninckel of Norway by 0.28 seconds to lead after the downhill.
Vonn's time was nearly two seconds quicker than 2014 Olympic slalom champion and pre-race favorite Shiffrin, but the 33-year-old still described herself as the "underdog."
"I'm just the old lady trying to hang on for a medal," she told reporters ahead of the slalom.
But it was not to be for the ski great, who had already become the oldest woman to win an Olympic alpine skiing medal with her downhill bronze Wednesday.
Throughout the last fortnight Vonn has said that these Games are likely to be her last and if that proves to be the case the veteran ends her Olympic career with three medals.
'Still feels good'
There was much focus on Shiffrin before the race as victory would have made her only the fourth alpine skier to win an Olympic gold in three different disciplines. But there is still time for the 22-year-old to match, and even surpass, that feat.
After the race, Shiffrin said she was happy with her Pyeongchang haul of gold and silver.
"It feels good. It's a nice way to end the Olympics. I started off with a bang, and ending with a medal on the podium is really cool," the three-time slalom world champion said.
"I came into these Olympics knowing I could be a medal threat in multiple disciplines. I didn't even know how many I would ski.
"After the gold in the giant slalom, I was really hopeful and positive. Then I had a tougher day in the slalom but it still feels good though."
Before the Games, there was much talk of Shiffrin, the overall World Cup leader and the most dominant female skier of recent seasons, competing in all five alpine events.
But with races postponed in the first week because of strong winds, the new schedule made such a task difficult and so she withdrew from the super-G and the downhill. She also failed to defend her slalom title.
Asked about the pressure of going for multiple golds, Shiffrin said: "It's a pressure I put on myself. But I have an incredible amount of support from fans, friends and family."