Macdermott held off Surrey Quest in a thrilling photo finish by a nose - the smallest of official winning margins - to add the latest chapter in Mullins' miraculous season.
Having won the Gold Cup and celebrated his 100th winner at the Cheltenham Festival last month Mullins then secured last weekend's Grand National at Aintree with I Am Maximus.
With the lure of emulating the legendary Vincent O'Brien - the last Irish trainer to claim the British National Hunt title in 1953/54 - Mullins sent over a strong team to Ayr on Saturday.
In the Scottish National itself Macdermott was joined by stablemates Klarc Kent, who came fourth, Ontheropes (fifth), Spanish Harlem (sixth), Mr Incredible (pulled up) and We'llhaveawan (unseated rider).
The six-year-old novice's battling success means that barring a dramatic change of fortune Mullins will be crowned champion next Saturday when the British National Hunt season officially closes, at Sandown.
Macdermott, ridden by Mullins' nephew Danny, took him over the three million pound prize money mark - £163,000 clear of Dan Skelton and £255,000 ahead of sitting champion Paul Nicholls.
"We've a bit to go yet and there's still a good bit of prize-money (at stake) but we're in pole position and it looks very good," said Mullins.
