Gillan, who has previously appeared in Doctor Who as a soothsayer in 2008 episode The Fires Of Pompeii, as well as in Rebus and The Kevin Bishop Show, will join Smith for the new series of the hit sci fi drama, which begins filming this summer and will air on BBC1 in spring next year.
However, the BBC has not yet revealed what her character will be called.
Smith, the 11th Time Lord, was announced as David Tennant's replacement in January. However, Tennant will still be seen in the role in three further Doctor Who specials that will air between autumn and the end of the year, as well as two episodes of spin-off show The Sarah Jane Adventures.
The BBC said Gillan beat dozens of hopefuls to land the role as the new companion. She follows in the footsteps of Billie Piper, Freema Agyeman and Catherine Tate as the Doctor's most recent sidekicks since BBC1's successful revival of the show over four series since 2005.
"I am absolutely over the moon at being chosen to play the Doctor's new companion, The show is such a massive phenomenon that I can't quite believe I am going to be a part of it. Matt Smith is an incredible actor and it is going to be so much fun to act alongside him... I just can't wait to get started."
"A generation of little girls will want to be her. And a generation of little boys will want them to be her too."
Piers Wenger, Doctor Who executive producer and head of drama BBC Wales, added: "We knew Karen was perfect for the role the moment we saw her. She brought an energy and excitement to the part that was just fantastic.
"And when she auditioned alongside Matt we knew we had something special. It is a partnership that is ready to take on the universe!"
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