The star, who has hosted both Broadway's Tony and TV's Emmy awards shows in the past, will front the 87th Academy Awards on February 22, said the Academy of Motion Picture Arts and Sciences.
The high-profile hosting job is a prime gig in Hollywood, at the climax of its annual awards season. Harris will follow Ellen DeGeneres last year and a who's who of showbiz over the decades.
"It is truly an honor and a thrill to be asked to host this year's Academy Awards," said the star of 2005's "How I Met Your Mother," in an Academy statement.
"I grew up watching the Oscars and was always in such awe of some of the greats who hosted the show," added Harris, whose latest film "Gone Girl" came out this month in the United States.
He added: "To be asked to follow in the footsteps of Johnny Carson, Billy Crystal, Ellen DeGeneres and everyone else who had the great fortune of hosting is a bucket list dream come true."
Producers Craig Zadan and Neil Meron said: "We are thrilled to have Neil host the Oscars. We have known him his entire adult life, and we have watched him explode as a great performer in feature films, television and stage.
"To work with him on the Oscars is the perfect storm, all of his resources and talent coming together on a global stage," added the pair, returning for their third Oscars show in a row.
Industry journal Variety noted that, with the Oscars job Harris will have done three of the four so-called EGOT full house of hosting duties -- the Emmys, Oscars and Tonys, with only the Grammys to go.
Harris, who hosted the Tony awards and the Emmys in 2009 and 2013, has been nominated for four Golden Globes and won five Emmys, including four for hosting the Tonys.
The Academy Awards are televised live in more than 225 countries around the globe. Organizers will announce nominations for the Oscars on January 15.
Hosting awards shows is more difficult and prone to pitfalls than many imagine.
Recent questionable Oscars hosts have included James Franco and Anne Hathaway who were widely panned in 2011, and Seth McFarlane whose "We saw your boobs' song raised eyebrows, not in a good way.
In 2012, veteran host Billy Crystal was brought in at the last minute after Eddie Murphy pulled out due to row about an anti-gay slur involving his producer Brett Ratner.
DeGeneres was widely praised for her slick performance, and also the infamous celebrity selfie photo and take-out pizza skit.
Over at the Golden Globes Tiny Fey and Amy Poehler have won plaudits for their hosting duties, following a few years of provocative British comic Ricky Gervais who raised some hackles in Hollywood.
The Oscars' Academy head Cheryl Boone Isaacs voiced confidence in Harris.
"He is the consummate entertainer. Neil's distinctive charm and showmanship make him the ideal host to honor the Oscar legacy and ensure we all enjoy another unforgettable celebration," she said.
"Neil is a terrific actor, singer, risk-taker and collaborator... We can't wait to see the show that he and Craig and Neil create together," she added.