Foreign Affairs Minister Simon Coveney has been named as the new Tánaiste.
Leo Varadkar made the announcement in the Dáil earlier on Thursday.
It follows Tuesday's resignation of Frances Fitzgerald as Tánaiste and Business Minister.
Minister Coveney is the Foreign Affairs Minister, and was Mr Varadkar's opponent for the Fine Gael leadership earlier this year.
The Cork-based minister will offer regional balance in Cabinet leadership - with Mr Varadkar from a Dublin constituency.
Explaining his decision, the Taoiseach said: “Appointing the Minister for Foreign Affairs and Trade, Simon Coveney TD, as Tánaiste will enhance his role in the Brexit negotiations currently underway and will make it easier for him to coordinate the work of other departments with respect of Brexit."
Heather Humphreys, meanwhile, has been announced as the new Business Minister - with Mr Varadkar saying her "experience as a minister and also her background in banking and finance makes her very suited to this role".
Dublin Rathdown TD Josepha Madigan will take over the Culture, Heritage and Gaeltacht portfolio from Minister Humphreys.
It will be Deputy Madigan's first Cabinet role, and comes less than two years after she was first elected to the Dáil.
Josepha Madigan. Photo: Sam Boal/Rollingnews.ie
President Michael D Higgins confirmed the roles during a ceremony at Áras an Uachtaráin in the Phoenix Park earlier.
Their new titles were announced as they received their seals of office.
<blockquote class="twitter-video" data-lang="en"><p lang="en" dir="ltr">At a ceremony at <a href="https://twitter.com/hashtag/%C3%81rasAnUachtar%C3%A1in?src=hash&ref_src=twsrc%5Etfw">#ÁrasAnUachtaráin</a>, President Higgins today appointed Heather Humphreys TD as Minister for Business, Enterprise and Innovation, and Josepha Madigan TD as Minister for Culture, Heritage and the Gaeltacht. <a href="https://t.co/jCzAHsrtLk">pic.twitter.com/jCzAHsrtLk</a></p>— President of Ireland (@PresidentIRL) <a href="https://twitter.com/PresidentIRL/status/936254477652328450?ref_src=twsrc%5Etfw">November 30, 2017</a></blockquote>
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Deputy Fitzgerald's decision to stand aside came after a week of criticism from opposition parties over her handling of an email in May 2015 which alluded to the Garda legal strategy against whistleblower Maurice McCabe.
A Fianna Fáil motion of no confidence in the former justice minister had threatened to bring an end to their confidence and supply agreement with Fine Gael - which would have seen the collapse of the minority Government.
However, Deputy Fitzgerald's decision on Tuesday to resign - only hours before the Fianna Fáil motion was due to be debated - averted a Christmas election.
Additional reporting: Jack Quann