Opelka had his serve broken twice in the opening set as Mannarino, a semifinalist in Long Island last year, took the first set with ease before the 21-year old claimed the final two sets.
Mannarino dominates first set
Mannarino made the initial breakthrough in the third game of the opening set as Opelka committed three unforced errors to hand the Frenchman double break point.
After saving the first, the American double faulted to gift Mannarino an early 2-1 lead. Opelka pushed the fifth seed to deuce, but the Frenchman ultimately held for a 4-2 advantage.
Mannarino then broke to love, the American committing a pair of errors off the ground. Suddenly firing winners, Opelka raced to a 0-40 lead on the Frenchman's serve, but a pair of aces and unreturnable serve gave the fifth seed the first set.
Opelka claims second set in tiebreaker
The 21-year old's serve started clicking, firing three aces in the first two games of the second set. Still not able to gain much traction on Mannarino's serve, Opelka was nonetheless out in front 4-3.
Finally with looks 0-30 and deuce in the Frenchman's next two service games, Opelka was undone by Mannarino's crafty play and some unusually big serving by the fifth seed.
The set would move along to a tiebreaker where the server won the first seven points, Mannarino hanging on to a slim 4-3 advantage, but Opelka would take four of the last five points to level the match at one set all.
Opelka makes early break stand up to advance
After each man held easily to open the final set, Opelka had the first break chance, but a slice of good fortune saved Mannarino. Given a second opportunity, the American drew a forehand error from the Frenchman to take a 2-1 lead.
The fifth seed had a look in the next Opelka service game, but the 21-year old's booming serve got him out of trouble. Mannarino saved a break point in his next service game to stay in touch.
The margin continued to be one break and Mannarino nearly made up the deficit, but an ace on break point by Opelka eventually led to a hold and a 5-3 lead. Serving for the match two games later, the American held to 15 to pick up a quality victory.