The 42-year-old Englishwoman is one of only nine women to ever take the green flag in the oval classic, finishing 22nd in 2012 and 26th in 2013 in her most recent IndyCar race.
Legge's best IndyCar results in 39 starts were sixth-place finishes at Milwaukee in 2006 and Las Vegas in 2007. She has been racing since 2014 in the IMSA SportsCar Championship.
"Racing at Indy with an Indy 500-winning team and with Honda is an amazing opportunity and one I'm very grateful for and intend to make the most of," Legge said. "I can't wait to get to work."
This year's race is scheduled for May 28 with qualifying the prior weekend.
The team, part owned by 1986 Indy 500 winner Bobby Rahal and retired talk show host David Letterman, won Indy 500 titles behind drivers Buddy Rice in 2004 and Japan's Takuma Sato in 2020.
American Danica Patrick has the best Indy 500 result by any woman racer, finishing third in 2009.