The 45-year-old American tennis icon and Fernandez, who was born three years after Williams won the first of her 14 Grand Slam doubles titles in 1999, defeated Russia's Ekaterina Alexandrova and China's Zhang Shuai 6-3, 6-4.
It is the first time Williams has reached a Grand Slam doubles quarter-final since 2016.
Williams is playing in the doubles after receiving a last-minute invitation from US Open organisers to play in the tournament she won twice alongside younger sister Serena.
The Williams-Fernandez pair could face top seeds Katerina Siniakova of the Czech Republic and American Taylor Townsend in the quarter-finals.
Williams later revealed that retired sibling Serena was "coaching from afar" as her big sister progressed through the doubles, and had called her earlier Monday.
"She told me, gave me a pep talk and made sure to call me today," Williams revealed. "I was, like, 'You're right. I got it. I got it.'
"She's definitely coaching from afar. She's so excited. She gets so nervous watching, and she's got the kids watching, they're all at home, just really on our side."
In her on-court interview after the win, Venus urged Serena to fly to New York to attend her quarter-final in person.
"If she came, it would be a dream for both of us and we'd have her on the court coaching," Williams joked. "We'd force her to hit, even though she doesn't hit often. It's probably best she doesn't come because we'd probably bully her."
The seven-time Grand Slam singles champion returned to competition at the end of July at the Washington Open after sixteen months away from the WTA Tour.
She indicated after her singles defeat that the US Open would likely be her last tournament of the season.