The second-seeded Radwanska came into this clash with Lepchenko 5-0 in their head-to-head, including a three set quarterfinal win en route to the final here last year.
Radwanska had to be looking forward to the start of her North American hardcourt swing, as 10 of her 13 WTA titles have come on hardcourts.
The Turning Point
Lepchenko rallied from a 3-1 deficit to win the first set. But Radwanska broke serve three times in the second set to level the match. A high-quality, back-and-forth third set saw Lepchenko hold, break and hold from 4-3 down to close out her 6-3, 3-6, 6-4 triumph.
By The Numbers
Lepchenko scored her third Top 10 win over World No.5 Radwanska, besting her previous Top 10 wins over World No.7 Sara Errani in 2013 Fed Cup play and over World No.6 Jelena Jankovic in Miami earlier this year. She is now into her first WTA quarterfinal since this event a year ago.
This was the first time in five Stanford appearances that Radwanska dropped her opener.
"I have a friend who is suffering from cancer whom I've known since I was 16," Lepchenko said. "He lives real close and always comes to my matches here. I wanted to win this one for him to give him a little inspiration to keep on fighting his illness.
"Even though I lost to Agnieszka many times before, I fought until the end, never let go and came out on top."