The Italian team, which has run each of the past five European F3 champions, has bought the entry of Lazarus for its entry to the series.
A move into GP2 has long been rumoured for Prema, which competed in the series' predecessor - Formula 3000 - for one season only in 1998.
Prema talked about a collaboration with Trident for the inaugural GP2 season in 2005, before deciding not to go ahead with the plan.
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Team manager Rene Rosin said: "Prema always followed the evolution of the GP2 concept as an interested spectator, and it is now finally time to join the game in first person.
"The move to GP2 is a logical step, following the successful experiences in the FIA Formula 3 European championship and in the Italian and the German Formula 4 championships, which will continue with the same level of commitment.
"I would like to thank [series boss] Bruno Michel for his efforts in making us part of the GP2 series".
Prema's 2015 F3 European champion Felix Rosenqvist was non-committal when asked about making the step to GP2 with the team.
"I only heard talks about it, and obviously the team wants me to be focused on Formula 3 for now," the Swede told AUTOSPORT.
"Rene has been a little bit secret about everything like that! We will have a chat soon, but the most important thing for now is to do a good job at Hockenheim [for the final Euro F3 round] and the Macau Grand Prix."
Other star Prema graduates still in the GP2 orbit include Ferrari junior Raffaele Marciello and Alex Lynn, winners of the 2013 European F3 title and Macau Grand Prix respectively, and GP3 ace Esteban Ocon, who claimed the 2014 Euro F3 crown.
Prema will continue to field a four-car European F3 team in 2016, as well as remaining in the Italian Formula 4 Championship.
Lazarus team principal Tancerdi Pagiaro said in a statement it was time "to follow new goals" after four years in GP2.
The earliest Prema alumnus to make it big in motorsport was Rinaldo Capello, who contested the 1985 Italian F3 Championship with the team before becoming an Audi legend and scoring three Le Mans 24 Hours wins (including one with Bentley).
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