Dellacqua made the third round in 2008, but since then, had not made it past the first round until she defeated Spaniard Lourdes Dominguez Lino 7-5, 6-3 on Tuesday.
The 29-year-old is nearing a career best ranking after a return to form over the past year. The left-hander sits at No. 48 in the world, with a career best of 39 in 2008.
She has not faced Safarova before.
Dellacqua has again teamed up with talented Australian teenager Ash Barty in the women’s doubles. She will be hoping to reach her first French Open doubles final since 2008 when she partnered with Italian Francesca Schiavone.