The number one seed won the first set but her young countrywoman fought back and forced a decider which went to an enthralling tie-break.
And the Charleston native secured her place in the semi-final with a 1-6, 6-4, 7-6(4) triumph.
Serena had beaten older sister Venus in another three-set clash on Thursday - and her first-round match against another American, Bernarda Pera, had also gone the distance.
WTA Lexington
Coco Gauff falls to Jennifer Brady in Lexington
15/08/2020 AT 23:25

Serena Williams pleased with tough test on WTA return

Rogers will now face Switzerland's Jil Teichmann, who beat Cici Bellis 6-2, 6-4.
Earlier in the day, Jennifer Brady defeated the conqueror of Johanna Konta, Marie Bouzkova, 6-1, 6-2.
Coco Gauff, the 16-year-old sensation, plays Ons Jabeur in the day's final match.
WTA Lexington
Serena Williams stunned by Shelby Rogers at Top Seed Open
14/08/2020 AT 23:00
WTA Lexington
Serena Williams survives scare to defeat sister Venus in epic comeback
13/08/2020 AT 20:38