He earned his Bachelor of Science from the University of Michigan in 1995, where he was president of the student government, and his Juris Doctor from Harvard Law School in 1998.

[5] In 2006, Greenberg met art collectors and investors Steve Wilson and Laura Lee Brown, and with them co-founded the 21c Museum Hotels chain.

[11] In January 2021, Greenberg and Matt Jones, a sports radio host, purchased a majority stake in Ohio Valley Wrestling.

[13][14] In April 2021, Greenberg announced his candidacy for mayor of Louisville in the 2022 election, seeking to succeed Greg Fischer, who could not run for reelection due to term limits.

[15] He ran on a platform of public safety, affordable housing, universal pre-K, cracking down on illegal guns, supporting abortion rights, and cleaning up the city.

[16] On February 14, 2022, Quintez Brown, a 21-year-old social justice activist and prominent voice in the Black Lives Matter community who was running as an independent for Louisville's Metro Council, walked into Greenberg's campaign headquarters office near downtown Louisville and allegedly fired several shots from a 9 mm Glock semi-automatic pistol at Greenberg from the doorway.

[30] Senate Minority Leader Mitch McConnell characterized the shooting as “what appears to be an assassination attempt against a Jewish mayoral candidate".