Flipkens lost in qualifying at Flushing Meadows but now will participate in the main draw for the 11th time.
Her best showing at Flushing Meadows was reaching the third round in 2009. She currently is ranked 109th.
Barthel is No. 102 and hasn't played on tour since losing her opening match at Lausanne, Switzerland, last month.
She was supposed to face Lesia Tsurenko in the first round at the U.S. Open.
The U.S. Tennis Association announced Barthel's withdrawal Sunday, a day before main-draw play begins.