Harry Maguire rose to the occasion as Manchester United handed Liverpool a fourth successive defeat with the England international securing a 2-1 win over the struggling Premier League champions on Sunday.
After defeats to Crystal Palace, Galatasaray and Chelsea, Arne Slot's side endured their most painful setback of the season at the hands of their bitter rivals.
Bryan Mbeumo put United in front after two minutes and although Cody Gakpo equalised in the 78th minute, Maguire secured his club's first win at Anfield since 2016 with an 84th minute header.
Liverpool dropped to fourth in the table on 15 points, four behind leaders Arsenal.
United, who won back-to-back league games for the first time under manager Ruben Amorim, climbed to ninth with 13 points.
"It means everything. They had had the better of us over the last few years and it's not been good for our club. We have not given our fans enough days like today, so it has been a long time coming, coming to this ground and picking up three points," Maguire told Sky Sports.
"It is not just three points to the club and to the boys. I have been coming to this ground for seven years now and to not get three points have been tough. It's for the fans and I hope they had a great night tonight."
Defeat leaves Slot still searching for answers in how to get the right blend after splashing out nearly £450 million on new players in the transfer market.
Liverpool had only lost one of the previous 14 Premier League meetings between the sides.
However, the Reds are in a state of flux after transforming the squad that stormed to the title last season and the tragic loss of Diogo Jota, who died in a car accident in July.
After three consecutive defeats for the first time in Slot's reign, Liverpool could barely have imagined a worse start.
Mbeumo sped past Virgil van Dijk with ease before firing past Giorgi Mamardashvili from Amad Diallo's pass after barely a minute.
The home side and support were furious that play was not stopped in the build-up after Alexis MacAllister went down with a head injury, inflicted by his own captain Van Dijk.
Slot left £100 million signing Florian Wirtz on the bench for the second consecutive game as he looked in vain to find the right balance between defence and attack.
Gakpo should have levelled for the defending champions when he hit the post from Mohamed Salah's through ball in Liverpool's one flowing move of the first half.
However, it was United who should have been further in front by half-time.
Bruno Fernandes spurned a glorious chance to double the Red Devils' lead when he hit the outside of the post when unmarked from the edge of the area.
At the other end, Senne Lammens was rarely troubled in the first 45 minutes, but produced a big save when called upon to deny Alexander Isak.
Gakpo's deflected cross then came back off the post and the Dutchman rattled the woodwork for a third time early in the second half.
Slot turned to his near £200 million in forward options off the bench as Wirtz and Hugo Ekitike were introduced on the hour mark to join Salah, Gakpo and Isak in a five-man attack.
Salah's lack of form showed in a wild finish to slice wide with just Lammens to beat at the back post.
Liverpool's wealth of attacking talent finally broke the door down when Federico Chiesa, who had replaced Isak moments earlier, drilled in a low cross that Gakpo converted from point blank range.
Yet, their defensive frailties meant parity only lasted six minutes as Maguire was left unmarked to head in Fernandes's looping cross.
