Lepchenko originally looked like she was headed for a straight set victory, building a 63 20 lead and even holding a point for 63 30. Jankovic flipped the script, taking eight games in a row - and 11 of the next 12 - to steal the second set, 6-2, and go up 5-1 in the third set. But the match turned again from there, as Lepchenko won five of the next six games to push it to a deciding third set tie-break.
The momentum was all Lepchenko's, and she would finish the No.7-seeded Jankovic, 63 26 76(2).
Lepchenko's win over the World No.6 was the best win of her career. It was the second Top 10 win of her career, having beaten a No.7-ranked Sara Errani during Fed Cup last year - and on clay too.
Other early upsets saw Barbora Zahlavova Strycova edge No.13 seed Roberta Vinci, 64 26 75, Elina Svitolina outdo No.18 seed Eugenie Bouchard, 16 61 62, and Ajla Tomljanovic rally from 63 52 down - and 4-1 down in the second set tie-break - to scrape past No.30 seed Garbiñe Muguruza, 36 76(6) 61.
Zahlavova Strycova's win over the No.14-ranked Vinci was the equal-best win of her career - the Czech also defeated a No.14-ranked Petra Kvitova in the early rounds of Indian Wells three years ago.
Meanwhile, No.2 seed Li Na, No.10 seed Dominika Cibulkova, No.22 seed Alizé Cornet, No.24 seed Kaia Kanepi and No.32 seed Elena Vesnina all advanced. Li didn't even have to take the court, receiving a walkover from Alisa Kleybanova when the Russian had to pull out due to a viral illness.
There was one other withdrawal, as Simona Halep - the No.6 seed - withdrew due to a toe injury.
"I'm very disappointed to have to withdraw today," Halep stated. "Two days ago I had surgery on my right big toe for an infected toenail. Obviously, on court, I need to push off a lot with my toe, and it's too sore. So unfortunately I need to withdraw as I am unable to play with this restriction I have."
"My next couple of events are Fed Cup and Stuttgart, and I should be fine by then."