Steps at Wick was painted in 1936 and shows the Black Stairs in Wick’s Pulteneytown area.
Auctioneers Bonhams said it was the first time in years that the painting had become available for sale.
Lowry, who grew up in Salford, was famous for his matchstick figure art and was a regular visitor to Scotland.
Bonhams said Steps at Wick could sell for £500,000 to £800,000 at an auction of British and Irish art on 20 November.
The image and occasion of this painting is commemorated with an engraved plaque of the painting at the site of the steps in Wick.
It bears the legend: “This is the original site where L.S. Lowry painted Black Steps, Wick in 1936.” Lowry used to holiday in Scotland during the 1930’s.
The steps pictured in Lowry’s image were part of Thomas Telford’s 1809 scheme for the new town plan of Pulteneytown for the British Fisheries Society.
The Black Stairs were part of Telford’s original plan for Pulteneytown linking the residential area above the bank, via Lower Dunbar Street, to the harbour below.
The steps were, however, not begun until the 1820s. Their name The Black Stairs appears to be a local, popular one as it does not feature in Telford’s plan.
An anti-establishment figure, Lowry holds the record for rejecting the most state honours, including a knighthood.
Lowry had an isolated upbringing in northern England. He spent many solitary early years in the leafy Manchester suburb of Victoria Park, Rusholm, later moving to the town of Pendlebury which was the inspiration for his industrial scenes.
He is particularly recognised for his trademark ‘matchstick men’ represented in desolate industrial and urban landscapes.
Penny Day, of the Modern British and Irish Art Department at Bonhams, said: “We are privileged and delighted to be offering such an important, striking Lowry which has not been available for over 20 years.
“With the market for the artist stronger than ever and alongside the interest in the current Tate exhibition, we expect collectors will seize the opportunity to acquire this early tour de force”.