Van Sant will present Promised Land, an ecological drama about fracking starring Matt Damon, Frances McDormand and John Krasinski at the 63rd Berlinale, taking place February 7 to 17.
In the film Damon plays a corporate salesman sent to an economically depressed rural town with the task of buying up drilling rights to the local citizens' properties, but comes up against a grassroots anti-fracking campaign.
The festival will also showcase new releases from South Korea's Hong Sang-soo and Ulrich Seidl of Austria.
Organisers of the first major European film festival of the year said Hong Sang-soo, a critics' favourite, would premiere Nobody's Daughter Haewon, the follow-up to his Cannes entry In Another Country starring French actress Isabelle Huppert.
Seidl, one of Europe's most controversial film-makers known for his frank takes on sex and exploitation, will enter the running with Paradise: Hope, the final picture in a trilogy, about a girl who falls in love with a man four decades her senior.
US animators Kirk De Micco and Chris Sanders will premiere the 3-D movie The Croods featuring the voices of Nicolas Cage, Emma Stone and Ryan Reynolds. It will appear in the main showcase but out of competition.
Also slated to screen are Romanian director Calin Peter Netzer's drama Child's Pose and Chilean-Spanish production Gloria by Sebastian Lelio.
The Berlinale Special section will present the documentary Redemption Impossible by Christian Rost and Claus Strigel, about a rehabilitation project in Austria for chimps used in pharmaceutical testing.
Award-winning Chinese director Wong Kar Wai will lead the jury handing out the Golden and Silver Bear prizes on February 16.
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And French film-maker and producer Claude Lanzmann, famous for his 1985 documentary Shoah, will be honoured with a lifetime achievement award at the event.
Italy's veteran film-makers Paolo and Vittorio Taviani won the Golden Bear this year for Caesar Must Die, a docu-drama about inmates staging Shakespeare at a high-security prison.