The personal healthcare products and consumer goods manufacturer has agreed a five-year deal on 6,000 sq ft at Airport City office 4M.
The 4M building is next to the airport ground transport interchange.
PZ Cussons, whose brands include Imperial Leather, Carex, Original Source and Charles Worthington, said that it had taken the new office space in order to facilitate delivery of a business improvement project to meet increasing international demand for its brands and products.
The company moved its international HQ to a 40,000 sq ft facility at Manchester Business Park in May 2010.
Brandon Leigh, chief financial officer at PZ Cussons, said: "This development demonstrates our long term commitment to Manchester, with 250 people already employed on site here; along with our innovation centre in Salford where new products are created, and a manufacturing facility, which produces 170m bottles a year.
"We believe that being based here is good for business as it enables us to bring together our employees from around the world who are working on an important global project."
The deal follows the recent announcement that the new Metrolink line to Airport City is set to open 12 months ahead of schedule, with line testing already underway.
Lynda Shillaw, divisional chief executive at MAG Property, said: "Enquiries have increased four-fold since the announcement that the new Metrolink line to Airport City will launch early, providing us with greater connections to more people across Greater Manchester, especially areas such as Salford, Bury and Oldham.
"PZ Cussons is a great international business that requires direct access to international and regional transport links. Its decision to bring together the international project team at Airport City campus demonstrates the high calibre of occupier the new development is proving attractive to, and we are delighted we could help PZ Cussons cement its presence in the region."
CBRE and WHR are the retained letting agents for 4M.