Latics were on the back foot for the majority as a strong United side took the opportunity of making a positive first impression on their new Portuguese boss.
Despite Will Grigg’s first appearance of pre-season, Latics couldn’t get their 28-goal top scorer anywhere near enough ball to do any meaningful damage.
And after a scoreless first half, the visitors secured the victory with two goals in the first 10 minutes of the second period.
First Juan Mata made the most of a rare error from Jussi Jaaskelainen to tee up former Latics loanee Keane within three minutes of the start.
Then fellow substitute Pereira’s turn and shot flew into the net to double the lead after 55 minutes.
Not even the late appearance off the bench of Nick Powell for his second Latics ‘debut’ could spark Latics into anything resembling a comeback.
And United recorded a repeat 2-0 victory from their 1999 friendly triumph which officially opened the-then JJB Stadium.
The Reds, lacking their Euro ‘16 contingent but still packed with internationals, unsurprisingly settled into their stride first as they attempted to impress their new boss.
Latics were indebted to skipper Craig Morgan for moving quickly and superbly intercepting a cross from Henrikh Mkhitaryan that almost allowed Memphis Depay an early sight at goal.
The same combination did find its way through midway through the first period but, with the goal gaping, Memphis could only poke well wide of the mark to the relief of the Latics rearguard.
Latics threatened for the first time as an attacking force just before the half-hour mark when sublime skill from Michael Jacobs took him past two would-be defenders.
However, his cross from the left was over-hit and sailed out for a throw in front of the United fans on the far side.
A neat passing move then released the unlikely figure of Dan Burn down the left, but the big centre-back’s cross couldn’t find Will Grigg in the middle.
United quickly resumed control and almost took the lead 10 minutes before the break.
Ander Herrera sent Warrington-born Jesse Lingard down the right, and his first-time cross found Mkhitaryan at the far post.
Having been the stand-out performer in the first-half, Mkhitaryan blotted his copybook by blazing well over the top from a great position.
Latics had a half-chance at sneaking an undeserved lead just before the interval, but Emyr Huws was too slow to realise the great shooting chance he’d found himself in, and the opportunity was quickly snuffed out.
Grigg made way for Craig Davies at the interval, with United making the first raft of changes to get some much-needed minutes into the legs of their players.
And within three minutes of the restart, two of those newcomers were instrumental in the first goal of the game - with more than a helping hand from Latics goalkeeper Jaaskelainen.
An attempted kick forward from the Finn was charged down by Mata, who unselfishly laid the ball square for Keane - who spent a short time on loan at Latics in 2013/14 - to slot into an empty net.
Mata almost doubled the advantage 10 minutes into the second half, but he could only stab wide after former Latics favourite Antonio Valencia had linked up well with fellow half-time sub Ashley Young.
Latics weren’t so lucky moments later when the visitors did make it 2-0, a superb turn and shot by Pereira flying into the net before Jaaskelainen could move.
The remainder of the game was merely a training exercise for United, with Latics doing their best to keep in touch without seeing anywhere near enough of the ball to threaten to pull one back.
The home fans were given reason to cheer 19 minutes from time when Powell emerged off the bench to make his second ‘debut’ for Latics, having been released by United earlier this summer.
Youngster James Barrigan also entered the fray, with Emyr Huws and trialist Ryan Taylor making way, but Latics were unable to make any further inroads on the United goal.
Latics: Jaaskelainen; Taylor, Daniels, Morgan, Burn, Warnock; Power, Perkins, Huws; Jacobs; Grigg.
Subs: Nicholls, Burke, Barrigan (for Taylor, 71), Lang, O’Brien, Whitehead, Gregory, Powell (for Huws, 71), Davies (for Grigg, 46), Cosgrove.