The 26-year-old becomes new head coach Rafael Benitez's first signing at the Stadio San Paolo following two successful seasons with Eredivisie club PSV Eindhoven.
The right-footed left winger played his first competitive games on loan from Gent with Eendracht Aalsts, where he scored four times before moving to AGOVV and notching 30 goals in three years.
A move to Utrecht followed and 16 goals in two seasons earned him a move to PSV in 2011.
Mertens scored more than a goal every two games for PSV, with a haul of 37 strikes from 62 appearances.
His time at the Philips Stadion also saw him lift the Dutch Cup and Dutch Supercup in 2012.
Mertens made his international debut in February 2011 and has since scored twice in 19 outings for his national side.