Around 50,000 spectators are expected to watch the 73-year-old Dundonian, one of the most high-profile supporters of Scottish independence, lead a 3000-strong parade of pipers, drummers, dancers and dogs from 45th Street to Sixth Avenue in Manhattan.
Cox has been given the “Grand Marshall” honour months after winning a Golden Globe for his portrayal of the New York media magnate Logan Roy in Succession.
The last season was partly shot in Scotland, with key scenes filmed at the new V&A museum in Cox’s native Dundee and at the Gleneagles resort in Perthshire.
The parade Cox will lead, which will be held for the 22nd time on April 4 is the most high-profile event staged during the annual Tartan Week festivities in New York.
Cox, one of Scotland’s leading stage and screen actors, started his career at Dundee Rep, his local theatre, when he was just 14.
He studied at the London Academy of Music and Dramatic Art in 1965 before joining the Royal Lyceum Company in Edinburgh.
He went on to make his name with the Royal Shakespeare Company and the National Theatre before securing his first major screen role in the movie Manhunter, in which he was the first actor to play Hannibal Lecktor.
His film and TV appearances include Rob Roy, Braveheart, The Bourne Identity, Zodiac, Rise of the Planet of the Apes, Super Troopers and Nuremberg.
Cox has compared his Succession character Logan Roy to King Lear, one of his best-known stage roles.
He only discovered that his character was born in Dundee towards the end of filming on the first series.
Cox is the first high-profile Scot to have been asked to lead the parade through Manhattan for a second time.
The actor said: “America holds a dear place in my heart, and to be able to celebrate my heritage and homeland of Scotland along with thousands of New Yorkers is a feeling unlike any other.”
Kyle Dawson, president of the National Tartan Day New York Committee, said: “We’re absolutely thrilled to welcome back Brian Cox as Grand Marshal of this year’s Tartan Day Parade.
“For 40 years, he has wowed the masses with his incredible acting – whether it be in his role as Hannibal in Manhunter or, most recently, his portrayal of media magnate Logan Roy.
"His love of America runs as deep as the love he has for his Scottish roots, making him the perfect Scot to lead our parade.”
Malcolm Roughead, chief executive of national tourism agency VisitScotland, said: “Brian Cox is a distinguished actor and a familiar face on the big and small screen, not least the award-winning HBO series Succession, which was partly filmed right here in Scotland.
"The parade is an important staple in the Scottish tourism industry calendar as a platform to promote Scotland as a must-visit destination to our largest international inbound visitor market.”