The Barony of Meldrum was originally the territory of Auchineve and was granted to Philip de Phendarg in 1236 by the Abbot of Arbroath during the reign of the Scottish King Alexander II. It is Sir Philip de Fendarg, the son, who is believed to have first carried the title of Meldrum, which was then spelt Melgdrum. A translation from the Gaelic of Meall Druim is: the ridge on the hill, which is appropriate given that the house was built on the only rocky outcrop on the highest point of the land. The original tower house was built around this time and forms the nucleus of all the later changes from the 17th, 19th and 20th Centuries which leave the house as it stands today. The Meldrum family became powerful and great landowners within the northeast of Scotland with properties including Drumoak and Fyvie Castle, which came into the family when Alexander Meldrum of Meldrum married the youngest daughter of Sir Henry Preston in 1433. Their son, George, was to become an Ambassador to the Court of King Henry VIII. William Meldrum, the last of the male line of the Meldrums, only had two daughters and, with the eldest married, it was Elizabeth, the youngest daughter, who was to inherit the estate of Meldrum, whilst Drumoak and Fyvie remained with other branches of the family.

Elizabeth's marriage to Sir William Seton brought the Seton family into ownership of the estate. William was the second son of Sir Alexander Seton, 1st Lord Gordon, however, William and his younger brother Henry were both killed at the Battle of Brechin on 18th May 1452. Their older brother, Alexander jr. (the Master of Gordon) took the name of Gordon and was to become 1st Earl Huntly. The estate of Meldrum passed to Sir William Seton's son, and was then to remain in the Seton family for a further 7 generations. It was the offspring of these Seton's that were to become Chancellors of Aberdeen, Chancellors of the St. Machar's Catherdral and of the University of Aberdeen, Chamberlain's to the Earl of Dunfermline and progenitors of the Setons of Pittmedden, of Mounie, of Belhelvie and others as well as extend the Seton family lands throughout the north of Scotland. William and Elizabeth's line at Meldrum ended with another Sir Alexander Seton. His eldest son, also Alexander, pre-deceased him in 1590, leaving a daughter Elizabeth, having been slain by James King of Barra. 

The Kings of Barra were long at feud with the Seton's of Meldrum, which feud might have been expected to come to a close towards the end of the 16th century when James King sold Barra to the Seton's.  But no; as late as 1615, Elizabeth Seton pursued at law James King "sumtyme of Barra' and others for being art and part in the slaughter of her father, Alexander, fiar of Meldrum, 'with schottis of hagbuttis and muscattis, commited upon the landis of Barra...' (the Braes of Bourtie). Alexander's second son, John Seton of Meldrum, succeeded but died in 1619 with no offspring from his marriage to Lady Grisel Stewart, daughter of the Earl of Atholl. Finally it was his 3rd son William who inherited Meldrum. However, as William's marriage to Anne Crighton of Fendraught was also childless, he bequeathed the Estate to his brothers' daughter Elizabeth in 1625 for her to inherit on his death. William Seton was responsible for the addition of the stone staircase in 1625 thereby creating the new entrance at the top of the stairs after blocking in the original archway to the internal courtyard. Also 1628 saw the addition of the original stable block including the central tower still prominent today with its feature of a stone-carved Royal Coat of Arms on the northeast face.

Elizabeth Seton married John Urquhart of Craigfintray, known as the Tutor of Cromarty in 1610, and she was eventually to inherit Meldrum Estate in 1635 on William's death and the estate passed to her son, Patrick Urquhart (she was the last Seton of Meldrum).  The Meldrum Estate was then to remain in the Urquhart family until 1898.