The Red Devils continued their recent surge with a convincing win over Brendan Rodgers' struggling side.
Wayne Rooney netted a ninth goal in his last eight appearances on home turf to give United a 12th-minute lead, 25 seconds after Raheem Sterling passed up a fine opportunity to put Liverpool ahead.
Louis van Gaal's men doubled their advantage in controversial circumstances after 40 minutes as Juan Mata stooped to score from Robin van Persie's flick — replays clearly showing the Spaniard to be offside.
Liverpool created the clearer openings over the course of the contest but poor finishing from Sterling and Mario Balotelli — plus another brilliant display from United goalkeeper David de Gea — served to frustrate it before Van Persie completed the scoring with a little over 20 minutes left.
The result piles more misery on Liverpool boss Brendan Rodgers, who saw his team crash out of the UEFA Champions League midweek, while for United, it acts as a measure of revenge for the 3-0 defeat suffered in last season's corresponding fixture.
Brad Jones played a first Premier League game in almost two years Liverpool as under-fire No. 1 Simon Mignolet dropped to the bench, where Balotelli was named having overcome a groin injury.
The intrigue in the United lineup came at the other end of the pitch as youngster James Wilson was selected to partner Van Persie up front, with Rooney playing a supporting role in an attacking lineup.
Marouane Fellaini collected a worryingly early booking for clattering through Adam Lallana but the England international recovered to thread a deft through ball for Sterling to draw a first save of the match from De Gea in the 12th minute.
United surged back at Liverpool immediately to open the scoring — Antonio Valencia nutmegging Joe Allen and picking out Rooney, who was afforded ample room to steer home side-footed from 16 yards.
De Gea held a deflected drive from Steven Gerrard as Liverpool looked to regain its footing and Sterling gave the Spain goalkeeper a more taxing save when he skipped past Phil Jones in the 23rd minute.
The visitors were then forced into a defensive change, Glen Johnson hobbling off to be replaced by Kolo Toure, and they fell 2-0 behind five minutes before the interval.
Ashley Young cut back to cross right-footed and Van Persie glanced on for Mata to nod home from an offside position, but the goal stood.
Balotelli came on for Lallana at the break and Jordan Henderson headed Sterling's left-wing center wastefully over as Liverpool sought a quick response.
Sterling then spurned his team's clearest opportunity of the match, allowing De Gea to block after Jonny Evans' wretched backpass sold his goalkeeper short.
Van Persie should have put the result beyond doubt after the hour when he side-footed wide from Valencia's excellent low delivery, and De Gea's finest moment arrived midway through the second period as he touched Balotelli's snapshot onto the crossbar with a stunning reaction save.
With 18 minutes remaining, Van Persie atoned for his earlier miss as Mata gave him a simple finish after Dejan Lovren woefully misjudged a clearance.
Balotelli was twice frustrated by De Gea from close range once more before Jones produced a save to compare with his opposite number's collection in the 87th minute, as Van Persie smashed toward the roof of the net.
Challenging for a top-four place to return to European football's top table next season looks an increasingly tall order for Liverpool, which sits ninth — 10 points behind United in third.