Having taken part in the show's 2015 Christmas special alongside Peter Capaldi and Alex Kingston, Lucas will reprise the role of River Song's former assistant Nardole.
"I'm chuffed to bits that Nardole is returning to the Tardis for some more adventures," Lucas said.
The star will appear in the opening episode of series 10, which begins filming in Cardiff on 20 June.
Steven Moffat, lead writer and executive producer, added he was "delighted and slightly amazed to be welcoming Matt Lucas back on to the Tardis - and this time it's not just for Christmas, he's sticking around".
"One of the greatest comedy talents on planet Earth is being unleashed on all of time and space."
Capaldi will return as The Doctor while Pearl Mackie replaces Jenna Coleman as his new companion, Bill, in her first major television role.
Lucas said he was looking forward to reprising his role in the sci-fi drama because he "loved acting with Peter and I'm excited to work with Pearl".
Also announced to be joining the series this year is Jekyll & Hyde and Sherlock star Stephanie Hyam.
Doctor Who will return to BBC One with a December Christmas special followed by a new series in 2017.

The move is the latest in a string of takeovers in Italy by cash-rich Chinese buyers.
The takeover gives ChemChina access to technology to make premium tyres and gives Pirelli greater access to the Chinese market.
Pirelli shares were 2.56% higher at €15.62 on Monday on the news.
ChemChina's tyre making unit, China National Tire & Rubber, is to buy the 26.2% stake in Pirelli owned by Italian investment firm Camfin. It will then launch an offer for the remaining shares.
Camfin said the bid would be launched by a consortium controlled by ChemChina but also part-owned by Camfin investors, who include Pirelli boss Marco Tronchetti Provera, Italian banks UniCredit and Intesa Sanpaolo, and Russia's Rosneft.
The offer will be launched at €15 per share, valuing the group at €7.1bn excluding net debt of almost €1bn.
Following reports of the deal on Friday, shares in Milan-listed Pirelli hit a 25-year high, closing at  €15.23.
Current Pirelli chief executive Tronchetti Provera, who started working for tyre maker in 1986 after marrying a member of the Italian family that founded the firm, will remain in his post.
Previous Chinese acquisitions in Italy include stakes in power grid firms Terna and Snam, turbine maker Ansaldo and luxury yacht maker Ferretti.
Matt Lucas is set to return to Doctor Who for its 10th series.
[NEXT_CONCEPT]
Chinese state-owned China National Chemical (ChemChina) is to buy Italian tyre maker Pirelli in a deal which values the firm at €7.1bn (£5.1bn).