After acquiring the 5,039-capacity West London venue just two years ago, HMV has now agreed to sell it to American-German live music joint venture Stage C for £32m.
Simon Fox, chief executive of the entertainment retailer, said: "The Hammersmith Apollo is an iconic London venue and it has been a privilege to own it over the last three years.
"However the sale will enable HMV to extend its bank facilities, strengthen its capital structure and ensure a strong future for the group."
The venue opened in 1932 as the Gaumont Palace cinema, before being renamed the Hammersmith Odeon in 1962.
It hosted a series of high-profile performances, including David Bowie's final show as his alter ego Ziggy Stardust in 1973, and was latterly the venue of the BBC's stand-up series, Live At The Apollo.
Stage C is jointly owned by London's indigO2 operator Ansco Music Club, part of US firm Anschutz Entertainment, and a subsidiary of Munich-based ticketing services provider CTS Eventim.
The sale of the Hammersmith Apollo is conditional on banking, shareholder and regulatory approval.
HMV has opted to sell the venue as part of plans to focus on its core retail business, with the proceedings going towards reducing its estimated £168m debt.
The struggling retailer recently surprised the financial markets by forecasting a return to profit in 2013, despite racking up losses of around £19m over the past financial year.