Humphries and brakeman Lotholz improved from a third-place standing after the first run down the 1,500-metre track at the Sanki Sliding Centre that features three tricky uphill sections into silver medal position with a two-run time of one minute 56.09 seconds.
"I made a few mistakes on that first run which cost us time, but that second run was good," said Humphries, who was making her first return to Sochi since winning her second-straight Olympic gold medal nearly one year ago.
The 29-year-old Humphries and her 22-year-old partner, fellow Calgarian Lotholz, finished second overall on the World Cup circuit with three bronze medals and a silver during the eight-race season.
For Humphries, Saturday's performance gives her three medals in as many trips to Sochi. She won Olympic gold a year ago as well as bronze at the Olympic test event in 2013.
It was the first trip to Sochi for rookie brakeman Lotholz.
"I was very proud of Melissa with our starts today," said Humphries in a statement released by Bobsleigh Canada Skeleton. "To come here and finish amongst these [American] women is awesome.
"It is a Happy Valentine's Day."
American Elana Meyers-Taylor locked up the overall title with her sixth victory of the season. Finishing second to Humphries and her Olympic brakeman, Heather Moyse, last year at the Sochi Games, the American got some redemption Saturday. Meyers-Taylor and Cherrelle Garrett cruised to the gold medal with a time of 1:55.48.
Compatriots Jamie Greubel Poser and Lauren Gibbs were third in 1:56.10.
Canadian men 4th
In the men's event, Justin Kripps of Summerland, B.C. and Edmonton's Bryan Barnett finished fourth with a combined time of 1:53.06.
"We drew No. 1 for the start order and managed to capitalize on the good ice," said Kripps. "We had our best two start ranks of the year and two solid drives.
"This track is really technical and it's quite different from any other track in the world. It is an amazing facility so I always get excited and it is a real pleasure to slide here."
The Canadians finished eighth in the overall standings.
Switzerland's Peter Rico and Simon Friedli won the race in 1:52.33. Latvia's Oskars Melbardis and Daumants Dreiskens were second in 1:52.46, while Beat Hefti and Alex Baumann, also of Switzerland, finished third in 1:52.60.
The Latvians claimed the overall title with 1,684 points, 48 ahead of Hefti and Baumann.
Calgary's Chris Spring and Derek Plug were 14th in 1:54.54 while World Cup rookies, Nick Poloniato of Hamilton and Calgary's Josh Kirkpatrick, finished 16th at 1:55.52.
The men's four-man races are scheduled for Sunday.