Filming took place from April to July 2015, in Rome, Italy. The film was released on February 12, 2016, by Paramount Pictures to generally negative reviews from critics and earned $56 million against a $55 million budget. A director's cut titled Ben Stiller's Zoolander 2, is in development for Paramount+.
At Fashion Interpol, a secret agent, Valentina Valencia examines the expressions of recently assassinated pop singers' last images and believes they match Derek Zoolander's signature look, "Blue Steel". A flashback reveals that Derek Zoolander Center For Kids Who Can't Read Good collapsed, killing Matilda and injuring Hansel. Derek later lost custody of his son, Derek Jr, and announced his retirement from modeling and subsequent reclusion.
Derek now lives alone in "extreme northern" New Jersey. Billy Zane visits and gives him an invitation to the House of Atoz fashion show by the "Queen of Haute Couture", Alexanya Atoz, and persuades him to return to a regular lifestyle in order to regain custody of his son. In the "uncharted Malibu territories", Hansel returns to his home after dinner and is informed by his orgy that they are all pregnant and that he is the father. He is later given the same invitation by Zane.
At the fashion show, Derek and Hansel are surprised to find that the ever-changing fashion world is now dominated by the likes of Don Atari and the non-binary All. They are put on the runway in "Old" and "Lame" outfits and are doused by a large bucket of prunes. Afterwards, Alexanya congratulates them on their performance.
After reuniting, Derek and Hansel are tracked down by Valentina, who asks them to help Interpol uncover who is behind the systematic assassinations. With Valentina's help, Derek discovers his son is residing at a local orphanage. They find him, but Derek is distraught by his son's obesity. After Matilda's ghost asks him to protect their son, Hansel convinces Derek to accept Derek Jr. After meeting the Headmaster, Derek takes his son around Rome. However, Derek Jr. becomes disgruntled with his father and returns to the orphanage.
Hansel receives an anonymous call, requesting that he travel to St. Peter's Basilica at midnight. He, Derek, and Valentina go to the church and meet with Sting, who tells them the tale of Adam and Eve and the little-known Steve, a secret that many popstars have died to protect. It is said that Steve is the common ancestor of all models and that he and his closest descendant Derek Jr holds the bloodline of the Fountain of Youth. Derek returns to the orphanage, only to find it in disrepair and his son and the Headmaster gone.
Mugatu tricks him into trading places with him so he can escape. Mugatu leaves on a helicopter while Hansel stows away by hiding on top of the rotor. Derek and Valentina swim back to Rome while Hansel infiltrates the House of Atoz. He witnesses Mugatu reuniting with Alexanya and killing Don Atari.
Hansel finds Derek Jr. imprisoned and reunites with Derek and Valentina at the IncrediBALL. They enter a bathhouse through a rear entrance and witness Derek Jr. strapped to a sacrificial table. Mugatu and many of the world's fashion designers prepare to cut out Derek Jr.'s heart and consume his blood, believing it to grant them eternal youth as it contains the blood of Steve. Derek, Hansel, and Valentina stop Mugatu from proceeding and he reveals that he brought together the world's fashion designers to kill them as revenge for leaving him imprisoned.
Alexanya, who is actually Katinka Ingaborgovinananananana in disguise, attacks Valentina, while Mugatu tells Derek that he was behind the destruction of his Center by hiring the construction crew to build a faulty base. He then throws an explosive towards the lava. Derek manages to stop it with "Magnum", but he struggles to keep it suspended in mid-air. Sting arrives and reveals that he is Hansel's father, and they, along with Derek Jr. releasing the look, "El Niño", successfully hurl the explosive back at Mugatu, presumably killing him in process.
Derek Jr. forgives his father for his mother's death and Derek and Valentina confess their love for each other. Matilda's ghost gives them her blessing and says that Mugatu live-streamed the event. Six weeks later, Derek and Hansel have returned to modeling. Hansel returns to living with his orgy and is now the father of 10 children. Derek and Valentina have a daughter named Darlene, while Derek Jr. becomes the next model and now in a relationship with Malala Yousafzai. As the end credits start rolling, Derek and Hansel celebrate their heroism with their friends, Derek's family, and a newly reformed Mugatu, who has survived from the explosion.
- Ben Stiller as Derek Zoolander
- Owen Wilson as Hansel McDonald
- Penelope Cruz as Valentina Valencia
- Will Ferrell as Jacobim Mugatu
- Cyrus Arnold as Derek Zoolander Jr.
- Kristen Wiig as Katinka Atoz
- Fred Arimsen as The VIP
- John Malkovich as Skip Taylor
- Milla Jovovich as Katinka Ingabogovinanana
- Benedict Cumberbatch as All
- Christine Taylor as Matilda Jeffries
- Kiefer Sutherland
- Billy Zane
- Justin Bieber
- Demi Lovato
- MC Hammer
- Neil deGrasse Tyson
- Katy Perry
- Ariana Grande
- The announcement for the movie came from a fashion show where Ben Stiller and Owen Wilson walked down the runway, in character, as Derek and Hansel.
- Eddie Murphy had expressed interest in being in this movie. He had even developed his own pose called "Black Iron".
- This is the twelfth film collaboration between Ben Stiller and Owen Wilson.
- Alexander Skarsgård, who played Meekus in Zoolander, made a cameo appearance as Adam in this movie.
- Both Zoolander films feature villainous fashion designers named after minor characters from Star Trek: The Original Series(1966). Ben Stiller is huge Star Trek fan.
- Jacobim Mugatu was named after a gorilla-like creature that appeared in season two, episode nineteen, "A Private Little .
- The House of ATOZ, and the character of Alexanya Atoz, can be linked to the character of Mr. Atoz, who appeared in Star Trek season three, episode twenty-three, "All Our Yesterdays".
- When Hansel and Zoolander are humiliated on stage towards the start of the movie, the outfits they are wearing are the same outfits as Mork from Ork's spacesuit on Mork & Mindy(1978). Likewise, in the next scene, a character uses Mork's catchphrase, "Shazbot". Mork was played by Robin Williams, who starred with Ben Stiller and Owen Wilson in the Night at the Museum film franchise, and who died a short time before this movie was filmed. The outfits are a little shout out to Williams.
- The teaser trailer was not narrated by Stephen Hawking, as many believe. It was narrated using a DECtalk (text-to-voice) machine, like the one Stephen Hawking uses.
- The film cast includes six Saturday Night Live (1975) cast members: Ben Stiller, Will Ferrell, Kristen Wiig, Fred Armisen, Kyle Mooney, and Beck Bennett.
- Fergie originally recorded vocals along with Akon and ASAP Rocky for a remix of the song "Relax" that appeared in the first movie. The final version of the remix that was used in this movie had Fergie and Akon's voices replaced with Nitty Scott and Sam Sparro.
- During the orgy scene with Hansel, Susan Sarandon quotes her famous song "Toucha Toucha Touch Me", from "The Rocky Horror Picture Show".
- Jerry Stiller's last film before his death in May 2020.
- Hansel tells Derek that "All my mom ever told me was my dad was a beat cop." Later we find out Hansel's dad is Sting, the former lead singer and bassist of The Police.
- When Hansel and Derek are in the car after arriving in Rome, vintage film is used to create the road scene behind them.
- This was not the first movie where Penélope Cruz played a character that encountered "The Fountain of Youth". Her character in Pirates of the Caribbean: On Stranger Tides (2011) also visited the fabled fountain.
- This was the second time Ben Stiller threw a knife and hit Owen Wilson in the leg. The first time was in "Starsky & Hutch"(2004).
- The director's cut, Ben Stiller's Zoolander 2, is in development for Paramount+.