Cortesio, 30, will be on the bases as part of the umpire crew when the Cubs play host to the Arizona Diamondbacks at HoHoKam Park. It's the first time a female umpire will work a Major League exhibition game in nearly 20 years.
"How do I feel about it? I could care less," Cubs pitcher Scott Eyre told The Associated Press. "If she can call a game, she can call a game."
A female umpire has never worked in the Major Leagues during the regular season. Pam Postema was the last woman to call big-league exhibition games, doing so in 1989.
"I'm looking forward to it," Cortesio told The Associated Press. "There will be a lot more people in the stands than I'm used to."
Cortesio, of Rock Island, Ill., is the only female umpire in professional baseball, and has been assigned to Double-A this year. This will be her ninth season overall, and fifth in Double-A. Triple-A and Double-A umpires routinely work Spring Training games.
"I was kind of expecting it," she said. "Umpires with my seniority usually get picked."
She has been working Minor League exhibition games this month in Arizona. Last July, Cortesio called the Futures Game for Minor League prospects, then worked the Home Run Derby at the All-Star Game in Pittsburgh.
She's been an instructor for several years at the Jim Evans Academy of Professional Umpiring, and is in line for a promotion to Triple-A when the next vacancy occurs.
"You always get asked if a woman can play in the big leagues," Cubs manager Lou Piniella said, "and the answer is no. Can a woman be an umpire? The answer is absolutely yes."
Thursday marks the first time Cortesio will work a game with a Major League umpire, joining Mike Winters' crew.
"I think I'm as excited about this as anything," she said.
Carrie Muskat is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.