The 83-year-old founding father and ex-leader of the Democratic Unionist Party is to relinquish the North Antrim seat he first won in 1970.
His decision could open the way for his son, Ian Paisley Jnr, to stand as the DUP's candidate in the constituency.
The contest is expected to be a tight one, with the leader of the hardline Traditional Unionist Voice party, Jim Allister, having already announced his intention to run in North Antrim. The DUP will officially select its Westminster candidate for the North Antrim seat next week.
Mr Paisley announced his decision to stand down in his local constituency paper, the Ballymena Guardian.
Ian Paisley Jnr confirmed his father would be standing down. "I would want to pay tribute to the fantastic role my father has played as a Member of Parliament for the last 40 years," he said.
Famed for his firebrand oratory, Mr Paisley was a founding member of the Free Presbyterian Church in Ireland in 1951. His evangelical theology heavily influenced his political views and throughout the Troubles he forthrightly denounced Catholicism and the Papacy.
During the conflict he was a fierce critic of power-sharing with nationalists and of the Republic of Ireland having a say in Northern Ireland's affairs. But in his later political life, the one-time cheer-leader for hardline unionism underwent somewhat of a political conversion which finally saw him enter office with his long-time enemy, Sinn Fein.
His decision to accept the position of First Minister alongside Deputy First Minister and former IRA commander Martin McGuinness in 2007 saw him hailed as a peacemaker by moderates but criticised by many former followers who accused him of betraying Ulster. What proved almost more remarkable was the warmth of the relationship the two erstwhile foes developed during their year in officer together, leading some to dub them the "Chuckle Brothers".
Mr Paisley stood down as First Minister in 2008. He was replaced by his long-time DUP deputy leader, Peter Robinson.
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