After breezing through the first set, the 20-year-old Ostapenko's nerves began to show and unforced errors helped the Lepchenko, 31, take the final two sets in tiebreaks.
Fan favourite Petra Kvitova, playing in just her 13th match since a knife injury to her hand inflicted by an intruder at her home, beat Spaniard Carla Suarez Navarro 6-1 7-6(5).
The Czech’s six aces and 32 winners were too much for the 28-year-old Navarro, who had no aces and just seven winners.
"I’m feeling pretty tired right now," said Kvitova, who was trailing 4-1 in the second set before winning the tiebreak.
"I’m trying to come back as soon as possible but it is just a matter of time," added the 14th seed.
MLADENOVIC OUSTED
Strycova reached the second round for the fourth straight year to leave 13th seed Mladenovic winless in four attempts on the Canadian hardcourts after the first match on an overcast centre court in Toronto lasted just 75 minutes.
"I started very well and felt good on court," said the 26th-ranked Strycova, whose only career title came in 2011 in Quebec City. "I was playing a lot of balls and being patient and I think that was the key in this match.
"In the second set she started to play a little bit better, she is a tough opponent. It is a great win for me."
Playing her first event since a first-round loss at Wimbledon, Strycova got off to blazing start by breaking the misfiring Mladenovic three times on her way to a 5-0 lead.
After a visit from her mother at the changeover, Mladenovic, who has reached the finals in four events this season, including a win in St Petersburg, buckled down and halted the slide with a break of her own and a hold of serve.
Given a second opportunity to close out the set, the Czech did not squander her chance.
The 31-year-old Strycova broke Mladenovic twice more to power ahead 4-0 in the second set, before her French opponent again offered some resistance and swept three straight games.
But the rally fizzled out as Strycova held and closed out the contest with a sixth break.
In other matches, Japan's Naomi Osaka advanced 6-1 4-1 when Britain's Heather Watson retired injured while Russian Daria Kasatkina, 20, battled past Italy's Roberta Vinci 7-6(3) 7-6(1).
(Reporting by Steve Keating in Toronto and Rory Carroll in Los Angeles. Editing by Larry King)
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