Clashes between the two sides over the years have been the subject of controversy on and off the pitch, from Kenny Dalglish's withering assessment of Ferguson in 1988 to Gary Neville's infamous celebration of a late goal at Old Trafford in front of the Liverpool fans in 2006.
The intensity between the two clubs is such that no player has transferred between Liverpool and United since Phil Chisnall left Old Trafford for Anfield in a £25,000 deal in 1964.
But how did the rivalry between the two clubs become so vitriolic?
While Celtic and Rangers will claim their rivalry is the most historic, the Liverpool-United hatred can be dated back to the industrial age before the end of the 19th century.
When the Manchester Ship Canal was built, it bypassed the port of Liverpool and payments to merchants in the city causing the loss of many jobs in Merseyside.
The football rivalry was mirrored inversely by the music scene in both cities. In the 1960s, The Beatles dominated the charts as the 'Mersey Beat' claimed everyone in its wake in the charts on both sides of the Atlantic.
While John, Paul, George and Ringo were taking the entertainment world by storm, Matt Busby was rebuilding his team to their 1968 European Cup crescendo.
Devastated by the 1958 Munich air disaster, which almost claimed his own life, Busby painstakingly built a new team and Bobby Charlton, George Best, Nobby Stiles et al conquered Europe with a Wembley victory over Benfica.
At the same time, another Scottish manager was performing his own brand of magic 40 miles down the road.
Second Division Liverpool were licking their wounds after an embarrassing FA Cup exit to non-league Worcester City when Bill Shankly was appointed manager in December 1959.
Shankly ordered a complete rehaul of the club's Anfield pitch, the Melwood training ground and his playing squad. In the days when managers were given time to make their mark, the Liverpool boss created a legacy which remained in place until the 1990s.
His time at Anfield culminated with the FA Cup in 1974 after claiming the league title and UEFA Cup in the previous season.
At the same time, United's fall from grace was spectacular and former Old Trafford favorite Denis Law backheeled them to relegation with his goal for Manchester City while Liverpool lapped up the silverware.
Shankly's legacy when he left Anfield in 1974 allowed Bob Paisley to dominate the English and European game. European Cups and league titles were rarely seen away from the club's trophy room.
At Old Trafford, a succession of managers such as Tommy Docherty, the late Dave Sexton and Ron Atkinson spent big but achieved little.
In the late 1980s, there was also a sea change in the music scene with Manchester boasting the likes of The Stone Roses, Happy Mondays, Inspiral Carpets and The Charlatans as the dominant forces. It would soon change on the football field, too.
In the penultimate game of the 1991-92 season, United needed a win at Anfield to keep alive their hopes of winning their first title since 1967 after Leeds crept ahead in the championship race earlier in the day. Instead, United and Ferguson were bombarded by the home supporters glorying in United's failure in a 2-0 defeat which sent the trophy to Elland Road.
Ferguson, almost in tears in a television interview after the 2-0 defeat, was not going to let it happen again. He guided United to the first Premier League title in 1993, leaving Liverpool trailing in sixth place and 25 points behind.
Ferguson never looked back, but Liverpool went into freefall under Graeme Souness with the FA Cup defeat by Bristol City at Anfield in 1994 representing the nadir of his tenure at the club.
Roy Evans and Gerard Houllier followed but, despite some cup success, the league title eluded the club. Even in the esteem with which Rafael Benitez is held by Liverpool fans, he was unable to break Ferguson's stranglehold on the Premier League, although the Spaniard's "fact" press conference is the stuff of legend.
Ferguson recorded a record 19th league title in 2011, finally completing his vow to knock Liverpool off their perch.
Can Liverpool ever regain the upper hand over United or is the dynasty set up by Ferguson at Old Trafford set to continue for years? Let us know what you think below.