The RAC is to relocate 300 employees to a new office in MediaCity.
The breakdown service and insurance giant has taken on 23,000 sq ft of space in Peel L&P's The Vic.
The move comes after the company put its Stretford call centre up for sale in February.
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The RAC will take on the entire second floor and part of the first at The Vic, which underwent a significant refurbishment three years ago.
The deal comes after videogames developer and publisher Team17 Digital committed to a further five years within the 6,000 sq ft ground floor space in The Vic, while the Department of Work and Pensions signed a 10-year deal for a 9,000 sq ft office space in Peel L&P’s neighbouring Alex building.
RAC chief executive Dave Hobday said: "We’re very excited by our move to Salford Quays and MediaCity as it demonstrates our continued long-term investment in the RAC, our colleagues and Manchester.
"The Vic’s best-in-class sustainability and well-being credentials offer colleagues a better working environment, first-class facilities and an all-round greater experience in a modern and vibrant city setting.
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"RAC colleagues will also be able to benefit from excellent transport links, parking, a host of shops on the doorstep, and plenty of eateries and bars for after-work socialising."
Simon Lovegrove, senior asset manager for Peel L&P, added: "We’ve seen a real flurry of activity in recent months with almost 40,000 sq. ft of lets in total across The Vic and Alex buildings which are experiencing a real renaissance in popularity.
"Occupiers are attracted by the buildings’ highly sustainable credentials, attractive waterfront setting and the vibrant MediaCity community with all of its amenities."
CBRE acted on behalf of RAC, Cushman and Wakefield acted for the Department of Work and Pensions and Canning O’Neill acted on behalf of Peel L&P at MediaCity.