As hurricane-force gusts battered the Republic of Ireland, the woman and one man died in separate incidents when trees fell on their cars.
The other man died in a chainsaw accident while attempting to remove a tree felled by the storm.
Across the island of Ireland, thousands of homes and businesses are without power and all schools have been shut.
About 360,000 homes and businesses in the Irish Republic, and 1,300 in Northern Ireland, are without power.
An amber warning for Northern Ireland, Wales, south west Scotland and the Isle of Man is in force until 23:00 BST.
The woman, in her 50s, died near Aglish, County Waterford. A female passenger, in her 70s, was injured. Her injuries were not believed to be life-threatening, the Gardai, Ireland's police force, said.
It urged all road users to stay indoors and not travel unless their journey was absolutely necessary.
The Met Office has warned of "potential danger to life", with wind gusts off the south coast of Ireland reaching 109mph (176km/h) at Fastnet Rock.
A yellow warning of "very windy weather" also covers parts of Scotland, the west and north of England and Wales.
"This is one of the strongest storms you're going to see this year."
It could be several days before power is restored to some homes in the Republic of Ireland, ESB Networks has warned.
The roof of Cork's football stadium has also been blown off by the winds.
In Wales, about 200 homes were without power and the Cleddau Bridge was shut to high-sided vehicles, Pembrokeshire County Council said. All schools in the county have been closed.
Elsewhere in the UK, skies have turned red and yellow as Ophelia drags dust from the Sahara through the atmosphere.
Ophelia has arrived from the Azores in the Atlantic Ocean and comes 30 years after the UK's Great Storm of 1987.
Ireland's Taoiseach Leo Varadkar said Ophelia was a dangerous storm and advised people to stay indoors until it had passed.
it would be the most severe storm to hit Ireland in half a century.
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The Irish Republic's Met Eireann said the storm was forecast to travel north over western parts of Ireland, with "violent and destructive gusts" of 75mph to 93mph (120 km/h to 150km/h) expected countrywide.
"There is a danger to life and property," it said.
It has issued a red alert for the country.
t has issued a red alert for the country.
In England, three flood warnings - meaning flooding is expected - have been issued in the South West, and there are 13 flood alerts - meaning flooding is possible - across other parts of the country.
The Scottish Environment Protection Agency has put a series of flood alerts and warnings in place for south west Scotland.
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