The 11-day Berlinale, one of the top three cinema showcases in Europe along with Cannes and Venice, will start with a gala screening of "Hail, Caesar!",
Joel and Ethan Coens' tribute to Tinseltown's 1950s golden age.
Clooney, who plays a dimwit actor in what the brothers have called the third in their "Numbskull Trilogy" with the heartthrob, is expected on the red carpet with his wife Amal and co-stars Channing Tatum and Tilda Swinton.
"Hail, Caesar!" which opened in the United States last week to rave reviews but modest box office returns, is screening out of competition at the festival.
Streep is serving as this year's jury president, judging 18 contenders from around the world.
The three-time Oscar winner and her team including British actor Clive Owen will on February 20 hand out the Golden Bear top prize, which last year went to Iranian dissident filmmaker Jafar Panahi for "Taxi", which he made in secret.
Among the world premieres generating buzz ahead of the start was a new adaptation of the international bestseller "Alone in Berlin", Hans Fallada's 1947 novel based on a true story.
The Nazi-era thriller sees Emma Thompson and Brendan Gleeson play a German couple who risk their lives to mount a resistance campaign against Hitler after losing their only son in the war.
The Berlinale Jury, headed by Meryl Streep Photo: DPA
Back to the roots
As Europe endures the largest refugee influx since World War II, with 1.1 million asylum seekers arriving in Germany last year, the theme of migration will be front and centre at the event.
Italian documentary director Gianfranco Rosi, who picked up top honours in Venice three years ago, will enter the competition with "Fire at Sea" about Lampedusa, a Mediterranean island on the front line of the crisis.
It will join another dozen films in the festival's sprawling sidebar sections looking at the impact of mass displacement in a globalised world.
"Refugees have always played a role at the Berlinale, since 1951," when the event was launched in the Cold War outpost of West Berlin just six years after World War II, festival director Dieter Kosslick told AFP.
"Back then many Germans were refugees and the festival was founded to foster understanding in German society and among nations."
In addition, hundreds of movie tickets have been set aside for asylum seekers at the festival, which will also launch donation drives at gala events to benefit refugee charities.
Biopics bonanza, movie marathons
Big crowds are also expected for "Genius", the feature debut by British theatre director Michael Grandage starring Colin Firth as literary editor Max Perkins, who published some of the 20th century's greatest American writers.
Jude Law plays Thomas Wolfe, Nicole Kidman his lover and muse Aline Bernstein, with Dominic West portraying Ernest Hemingway and Guy Pearce as F. Scott Fitzgerald.
Biopics will enjoy top billing, with Germany's first feature production on teenage diarist Anne Frank, who died at the Bergen-Belsen concentration camp, due to premiere.
US actor Don Cheadle will be in town to show his directorial debut, "Miles Ahead", in which he plays the jazz great Miles Davis.
And "Sex and the City" star Cynthia Nixon will unveil her portrayal of iconic American poet Emily Dickinson.
Kosslick, 67, said a further trend was marathon movies, testing the boundaries of storytelling in a world in which viewers had lengthened their attention spans by binge-watching ambitious new television series.
"There are feature films that really take their time to tell a complete story," he said.
One extreme outlier is a more than eight-hour-long Filipino historical opus, "A Lullaby to the Sorrowful Mystery" by Lav Diaz, which will be shown with just one hour-long break.
However "Lullaby" isn't even the longest feature that will test the stamina of cinema-goers.
"Chamisso's Shadow", based on the life of German 19th century scientific explorer Adelbert von Chamisso, weighing in at more than 12 hours, will be screened in a single sitting, with two intermissions.