Two-time defending champion Martina Navratilova defeated Chris Evert in the final, 6–2, 6–2 to win the singles tennis title at the 1988 Virginia Slims of Chicago. This was the 80th and the last time these two legends faced each other in a professional match, with Navratilova ending their rivalry 43–37 in her favour.
Seeds
A champion seed is indicated in bold text while text in italics indicates the round in which that seed was eliminated. The top four seeds received a bye to the second round.
Martina Navratilova (champion) Chris Evert (final) Gabriela Sabatini (quarterfinals) Manuela Maleeva (semifinals) Helena Suková (semifinals) Natasha Zvereva (second round) Zina Garrison (quarterfinals) Claudia Kohde-Kilsch (first round)