Stosur's career highlight came at the 2011 US Open when she claimed the first, and only, Grand Slam trophy but the 2013 tournament is already over for the Australian No. 11 seed after a shock loss to world No. 296 Duval.
The 17-year-old American had to qualify just to book a place in the main draw at Flushing Meadows and surely would have just been hoping to be competitive and not embarrassed by the 29-year-old Stosur when they walked onto Louis Armstrong Stadium.
Stosur then won a tight opening set 7-5, but the young American then took advantage of a struggling Australian to end up claiming the second and third sets 6-4, 6-4.
Stosur hit 10 double faults for the match, 56 unforced errors and won just 41 per cent of her second serves while able to only capitalise on 5-of-16 break points.
Duval will now take on Slovak veteran Daniela Hantuchova, who recorded a 7-5, 6-2 win over American Maria Sanchez.
Australia's other woman in action on Day 2 was Casey Dellacqua and despite a bright start, she lost 3-6, 6-1, 6-4 to Croatian Ajla Tomlijanovic just three weeks after her partner Amanda welcomed the couple's first baby into the world.
Other first round women's winners on Day 2 action included Petra Kvitova, Caroline Wozniacki, Victoria Azarenka, Sara Errani, Ana Ivanovic, Svetlana Kuznetsova and Maria Kirilenko.
The biggest women casualties of the day along with Stosur were Dominika Cibulkova and Nadia Petrova.
Seventh-seed Kvitova had a hiccup in the second set against Japan's Misaka Doi but the Czech eventually prevailed 6-2, 3-6, 6-1 to book in a second round clash with Serb Bojana Jovanovski who beat German Andrew Petkovic 6-2, 6-4.
Former world No. 1 Wozniacki beat China's Ying-Ying Duan 6-2, 7-5 to advance to the second round also where the Dane will take on South African Chanelle Scheepers who downed compatriot Chanel Simmonds 2-6, 6-2, 6-1.
World No. 2 Azarenka was in the last match up on Arthur Ashe Stadium and while her scoreline of 6-0, 6-0 over German Dinah Pfizenmaier looks brutal, her opponent actually played much better than that despite her 27 unforced errors and going 0-of-3 on break points.
The Belarusian who lost last year's US Open final to Serena Williams and has now started her campaign this year off well setting up a second round battle with Canadian Aleksandra Wozniak who beat Serb Vesna Dolonc 7-5, 7-6 (5).
Italian No.4 seed Errani recorded another double bagel scoreline thrashing Austrian Olivia Rogowska to book in a second round match-up with another Italian veteran Flavia Pennetta who advanced by downing American Nicole Gibbs 6-0, 6-2.
Another former world No. 1 Ivanovic had no trouble downing Georgia's Anna Tatishvili 6-2, 6-0 to see the Serb 13th-seed set up a second round match-up with Romanian Alexandra Dulgheru who beat American Varvara Lepchenko 6-7 (5), 6-2, 7-6 (5) in a three-set thriller.
American Christina McHale beat German Julia Goerges 6-4, 6-3 to move through to the next round where she will face the Ukraine's Elina Svitolina who upset Slovak 17th-seed Cibulkova 6-4, 6-3.
Russian veteran Kuznetsova, who won the 2004 US Open, is also through to the second round after beating American Mallory Burdette 6-3, 7-5. The 28-year-old two-time Grand Slam winner next plays China's Shuai Peng who beat Austrian Yvonne Meusburger 6-3, 6-4.
French 26th-seed Alize Cornet also cruised into the next round after beating Portugal's Maria Joao Koehler 6-3, 6-2. She will now play Tomlijanovic in the second round after she beat Dellacqua in three sets.
Romania's No. 21 seed Simona Halep who won in three sets over Brit Heather Watson 4-6, 6-4, 6-2. Halep next faces Croatia's Donna Vekic who won her first round clash with Mariana Duque-Marino 7-6 (5), 4-6, 6-2.
American wildcard Alison Riske upset Bulgarian Tsvetana Pironkova 6-3, 6-3 to set up a second round match-up with German 28th-seed Mona Barthel who downed Swede Johanna Larsson 6-1, 6-4.
Another experienced Italian is also through to the second round with No. 10 seed Roberta Vinci beating Hungary's Timea Babos 6-4, 6-2. Vinci next faces Czech Lucie Safarova who downed Ukrainian Lesia Tsurenko 6-3, 2-6, 6-4.
Russian 14th-seed Kirilenko thrashed Belgian Yanina Wickmayer 6-1, 6-1 as she now looks forward to a second round match against Portugal's Michelle Larcher de Brito who advanced by beating Greek Eleni Daniilidou 6-4, 6-3.
Another American wildcard advanced with Sachia Vickery beating Croatia's Mirjana Lucic-Baroni 6-4, 6-4 and she now next faces Israel's Julia Glushko who upset Russian veteran Petrova 6-3, 6-4.
A fourth Italian woman won their opening round match with Karin Knapp downing American Grace Min 6-3, 6-1 to set up a second round clash with Russian Elena Vesnina who beat German Annika Beck 6-1, 6-1.
A fifth Italian advanced when Camila Giorgi beat Slovak Jana Cepelova 6-2, 6-2 to set up a second round match-up with Chinese Taipei's Su-Wei Hsieh who beat Czech No. 31 seed Kiara Zakapalova 6-3, 6-3.