"I am opting out due to uncertain health conditions and regulations and all the other opt-outs in football right now," he said in a video posted to his Instagram account.
He said he will focus on preparing for the NFL draft.
Farley's mother died in 2018 from breast cancer.
"I cannot afford to lose another parent or loved one," he said. "Though the competitor in me badly wants to play this season, I cannot ignore what's going on in my heart and I must make the decision that brings me the most peace."
Farley, a junior, had four interceptions last season and has six in his college career. He was a first-team All-ACC selection and led the conference with 16 passes defended last season.
ESPN's Mel Kiper Jr. has a late first-round grade on Farley, who is ranked among the second tier of corners for the 2021 draft.
ESPN's Adam Schefter and Andrea Adelson contributed to this report.