The number 13 seed from Serbia - runner up at last year's tournament - had chances to win the match with several match points but she failed to take them, allowing Peng to capitalise and book a second-round meeting with either Roberta Vinci or Madison Keys.
Also falling at the first hurdle at the Lindner Family Tennis Center was 14th seed Francesca Schiavone, who was soundly beaten 6-1 6-3 by fellow Italian Camila Giorgi.
The only other seed in action on Monday, Dominika Cibulkova, was more successful, the Slovakian 11th seed beating Akgul Amanmuradova of Uzbekistan 6-3 6-4.
Other winners on the opening day of action in Ohio included Pole Urszula Radwanska, German duo Julia Goerges and Mona Barthel, Anabel Medina Garrigues of Spain and Greek player Eleni Daniilidou.
The Williams sisters, Venus and Serena, take their bow at the tournament on Tuesday.
- Lindner Family Tennis Center
- Roberta Vinci
- Madison Keys