The former First Minister's retirement announcement after 40 years of holding the seat clears the way for his MLA son to take on ex-party colleague Jim Allister.
The General Election showdown between Ian Paisley jnr and the Traditional Unionist Voice leader promises to be a bruising encounter that will have a major bearing on the future direction of unionism.
As tributes poured in for the 83-year-old former DUP leader yesterday following his announcement that he is stepping down, attention was last night already starting to turn to the intriguing contest to fill the seat of a man who has dominated politics for decades.
A polling day date has yet to be set by the Prime Minister and the formal selection of the DUP's North Antrim candidate will not take place until next Monday.
But Mr Paisley jnr appears to be guaranteed the nomination, and the campaign is already as good as under way.
He will defend his father's majority of almost 18,000 from 2005. But the political landscape has changed since then, with the DUP's decision two years later to enter a Stormont Executive with Sinn Fein.
Mr Allister quit the party in protest at that move, and will see the North Antrim contest as a major opportunity to destabilise power-sharing.
The DUP will continue to hit back, accusing him of having no alternative and effectively seeking a return of direct rule.
The TUV leader and former MEP was quickly on the attack yesterday. “North Antrim, I believe, will be looking for an MP with integrity and sound judgment. If Ian Paisley jnr is a candidate then the capacity for sound judgment will be a particular issue,” Mr Allister said.
He also cited controversies surrounding Mr Paisley jnr over his links to developer Seymour Sweeney and his approval for the secondment of PSNI personnel to train Libyan police.
While praising Mr Paisley snr's past record as a “towering Parliamentarian”, the TUV leader said the former First Minister's legacy would be “terrorist-inclusive government” at Stormont.
Mr Paisley jnr retorted, accusing his ex-colleague of continuing a “tirade of personal name calling and abuse even of an 83-year-old man”.
The DUP MLA said: “Jim Allister's trade in smear won't put bread on anyone's table. His personalised attacks directed at Dr Paisley and me won't attract extra jobs. His mud-slinging won't help the families struggling to make ends meet.
“Allister has nothing to say on the issues that matter: jobs, health, education, agriculture. Instead all he offers is character assassination directed at me. In fact, I don't think I've heard him say anything pleasant in public life about anyone.
“Not only is such behaviour underhand, but it is not what the public wants. I believe the people want and deserve better than the mud-slinging Allister offers.”