On His Own (12-1) became just the third horse to win the Goffs Thyestes Chase twice with a gallant all-the-way effort.
Carrying a big weight, Mullins' 10-year-old was given a bold sight at his fences by Paul Townend and it sparked him back to life.
Having been slightly below par over the larger obstacles this season, the Graham and Andrea Wylie-owned chaser went into the record books alongside Priests Leap and Wylde Hide.
Those two managed to win successive renewals but On His Own won back in 2012.
Los Amigos gave favourite backers a good run for their money but was six lengths adrift at the line.
Oscars Business was third with Balnaslow, a stablemate of the winner, fourth.
Walsh chose to ride Vesper Bell but he was well beaten.
Mullins said: "I thought Vesper Bell's form entitled him to win this so I advised Ruby to ride him.
"It's great to win this race again as it's our local track and I'm very pleased to equal Tom Dreaper's record of five wins.
"The Grand National has been his goal for the last two seasons and even though he has fallen twice it will have no bearing on whether he runs in it again. If you're not in, you can't win.
"If another big race comes along for him before the National he may run in it, though.
"I said to Paul I wanted to hear Des (Scahill, commentator) say that he jumped the first in front and he did, they were the only instructions I gave him.
"Balnaslow ran well and we'll try to find a nice race for him in the spring."
On His Own is 25-1 from 33s for the Grand National at Aintree in April.