The Regiment first mustered near Berwick in 1650 comprising five of Sir Arthur Hazelrigg's companies from Newcastle and five of Colonel Fenwick's companies from Berwick. The new Regiment was officially known as Monck's Regiment of Foot, and soon marched into Scotland and fought with distinction at the Battle of Dunbar on 3 September 1650. The earliest service which the Regiment can claim against a foreign power was in 1652, under Colonel Monck, who as one of three Admirals led the British Fleet with conspicuous success against the formidable Dutch Navy. The connection with the sea was furthered in 1664 when 500 men from the Regiment were raised by Royal Warrant for sea service, thus forming the Royal Marines.

On 1 January 1660, General Monck led the Regiment from Coldstream on his historic march to London, which they reached on 3 February. The Regiment were at once ordered to take up their quarters in the precincts of St James's Palace and were ordered by Monck to restore order and repress the riots which had characterised the last months of Parliamentary rule. As the exiled King Charles II returned to London in May that year, the Regiment were inspected by the Sovereign for the first time. His Majesty expressed himself as 'Much struck by the beauty, discipline and martial appearance of the Troops'.

On the King's Restoration, the disbandment of Cromwell's New Model Army was decreed by Act of Parliament, with the reservation that the Captain General's (Monck's) own Regiments of Horse and Foot be retained to the last. By January 1661 the disbandment of the Army was almost complete, save for Monck's Regiment of Foot. On 6 January a serious uprising occurred in London, necessitating the Regiment to be deployed to quash the riots. Following this it was decided to retain the Regiment permanently, for the personal security of the Sovereign. The King, however, already had his own bodyguard which had been formed abroad in 1656 during his exile. This, the First Regiment of Foot Guards, subsequently became the Grenadier Guards.

On 14 February 1661 the Regiment paraded at Tower Hill where they were ordered to ground arms as the Lord General's Regiment of Foot Guards, and immediately take up arms in the name of the King. The Regiment was offered the title of the Second Regiment of Foot Guards, but, being older than the First, refused and instead became The Coldstream Regiment of Foot Guards, to commemorate its march form Coldstream to London. As a result of this, and the Regiment's high standards, the regimental motto is Nulli Secundus (Second to None), but the Regiment takes second place after the Grenadiers in order of seniority and all ranks wear buttons in twos on their tunics.

From 1682 until 1993, the Regiment consisted of two battalions. The 3rd Battalion was formed in 1897 until it was placed into suspended animation in 1959. The 4th Battalion was formed during both world wars, and the 5th and 6th Battalions during World War 2. The 2nd Battalion was placed in suspended animation in 1993, although its colours continue to be borne by No.7 Company, the Regiment's independent incremental company stationed in London.

The Regiment has served with distinction in almost every campaign fought by the British Army - in the Peninsula Campaign, at Waterloo, and in both world wars. Every December the Regiment still celebrates its defence of Hougoumont Farm at Waterloo, with a brick from the farm being paraded around barracks by the Sergeants' Mess. In recent years the Regiment has been deployed to Northern Ireland, the Gulf, Bosnia, Iraq and Afghanistan. Thirteen members of the Regiment have been awarded the Victoria Cross, and one the George Cross.

Soldiers from the Regiment are traditionally recruited from the north east of England (from where the first soldiers in the Regiment came) and from the south west of England (from where Monck came). Despite its name being from a Scottish town, the Regiment is fiercely English and celebrates St George's Day in style each year.

The 1st Battalion's recent tour of Afghanistan on Operation HERRICK 11 (2009-10) was arguably its hardest fought campaign since World War 2. Engagements with the Taliban occurred on a daily basis, but the overarching threat was from improvised explosive devices, which restricted freedom of movement and hampered progress throughout the area of operations. The Battle Group was responsible for introducing the Afghan National Army and Police to its area, and by the end of the tour British troops, Afghan soldiers and Afghan policemen were of equal number across its area.

While the 1st Battalion was in Afghanistan, Number 7 Company recreated Monck's historic march from Coldstream to London in 25 days, through deep snow and freezing temperatures in January 2010.

The world-famous Regimental Band has recently released two best-selling CDs - Heroes, and Pride of the Nation.