When Ferguson arrived at Old Trafford in 1986 he famously said he wanted to knock Liverpool "off their perch" as the dominant force in English football but it took a long time to achieve it.
Liverpool won the league in 1988 and 1990, and were runners-up in '87 and '89, with only 1988, when United finished second, seeing Ferguson's side pose a real threat.
However, as Liverpool's star waned, United's rose and, after Arsenal, Leeds United and Blackburn Rovers took turns at the top, the balance of power in the north-west began changing.
Once United finally won the inaugural Premier League title in 1993 it was game over on the domestic front.
Liverpool, who have not topped the standings for 23 years, have watched United slowly but surely chip away at their record 18 titles until overhauling it in 2011 and moving on to 20 this year.
Although Ferguson regularly exchanged "pleasantries" with Rafa Benitez, often getting under the Spaniard's skin, the rivalry was probably at its most intense in Ferguson's first five years at United when Kenny Dalglish was desperately trying to prevent Liverpool's fall from grace.
The two Scots were united, however, after the Hillsborough stadium disaster, when Ferguson gave immediate support and did his utmost to ensure United's fans followed suit, sending a group to Anfield to pay their respects.
"As long as I live, I'll never forget Fergie's exceptional gesture," Dalglish wrote in his autobiography.
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It is one of the most iconic pieces of British sporting TV footage ever seen, as Newcastle United manager Kevin Keegan lost his temper live on air as the battle for the 1996 title moved into the home straight.
"I've kept really quiet, but I'll tell you something - he went down in my estimation when he said that,' an emotional Keegan ranted in reference to Ferguson's claim that teams tried harder against United.
"I'll tell you - you can tell him now, he'll be watching - we're still fighting for this title... and I'll tell you honestly, I will love it if we beat them - love it!"
Newcastle, who had been 12 points clear, fell away at the finish and United won the title by four points. Ferguson's reputation for winning "mind games" was cast in stone.
Newcastle were second again the following season but Keegan had resigned midway through the campaign and they disappeared from United's radar for good.
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During the late 1990s and early 2000s the Premier League was a two-horse race between United and Arsenal and in Arsene Wenger Ferguson had a rival who was not about to fall at his feet.
The cerebral Frenchman was certainly irritated by his opposite number but generally maintained his dignity while often the players of both sides were losing theirs in a series of high-octane clashes.
Ferguson had set the tone on Wenger's arrival at Arsenal from Japan in 1996. "They say he's an intelligent man, right? Speaks five languages? I've got a 15-year-old boy from the Ivory Coast who speaks five languages," he said.
When Wenger voiced his opinion that the fixture list was skewed in United's favour, Ferguson responded by calling him a novice, adding: "He should keep his opinions to Japanese football."
As the rivalry flared into the new century, Wenger finally let loose, saying: "Ferguson does what he wants and you (the press) are all down at his feet. He doesn't interest me and doesn't matter to me at all."
The enmity eventually cooled, helped no doubt by Arsenal falling away and no longer offering a challenge, and Ferguson's retirement leaves Wenger as the Premier League's longest-serving active manager.
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Ferguson took an instant dislike to Jose Mourinho when the upstart Portuguese coach famously slid down the Old Trafford touchline to celebrate his Porto side knocking United out of the Champions League in 2004.
So when Mourinho took over at Chelsea and finally another club was able to better United's finances, it was no surprise that their rivalry developed quickly.
Having seen off the challenge of Arsenal, suddenly it was Chelsea spoiling Ferguson's fun and, in Mourinho, who led the arriviste Londoners to successive league titles, he had a worthy foe on and off the pitch.
Mourinho said all the right things about his respect for Ferguson, then did all he could to show he did not care a jot, revelling in the battle of words and wit.
Ferguson could not seem to shake the younger, confident, charismatic rival and only when Mourinho left Chelsea did the Scot regain his position as the unquestioned top dog of the Premier League pack.
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For more than two decades Ferguson had paid little attention to Manchester City, even when he was on the receiving end of a 5-1 thrashing three years after his arrival.
Their transformation into one of the richest clubs in the world changed all that. Ferguson famously played down their chances by describing them as "noisy neighbours" and dismissed them as "a small club, with a small mentality."
However, City's bottomless budget eventually meant Ferguson had to take them seriously and, when the light blue half of Manchester finally got to celebrate the league title in 2012, with a 6-1 thrashing of United at Old Trafford along the way, it was clear there was a rivalry to take seriously.
City's Italian manager Roberto Mancini, like Mourinho a suave European with seemingly little interest in Ferguson's rants, duly became enemy number one and gave the Scot new focus as he entered his eighth decade.
Just like all others before him though, Mancini eventually slipped back, forced to claim his side were as good as United even as Ferguson celebrated another title having resumed the place from where he finally decided to retire - at the top.