Veteran midfielder Scholes converted from close range in the 51st minute before Mexican striker Javier Hernandez added United's second from Buttner's assist 12 minutes later.
Dutch defender Buttner, signed last month from Vitesse Arnhem, extended the lead with an impressive solo effort in the 66th minute, and Powell, a summer arrival from Crewe, added a fourth in the 82nd minute having come off the bench.
The hosts had been controversially awarded an early penalty when Ali Al Habsi was judged to have fouled Danny Welbeck, with justice seeming to be done as the Oman shot-stopper kept out Hernandez's attempt from the spot.
United's win takes them up to second in the table on nine points, one point behind leaders Chelsea, whose 100% start to the league campaign came to an end as they drew 0-0 at QPR.
There had been considerable focus on what happened before kick-off at Loftus Road, with Hoops defender Anton Ferdinand rejecting the offer of John Terry and Ashley Cole's outstretched hands at the pre-match handshake.
It was the first time that Ferdinand and Terry had met on a football field since the Chelsea and England centre-back's race trial in July, where Cole testified as a character witness for his Blues team-mate.
Terry was found not guilty of using a racial slur against Ferdinand following an incident in the corresponding fixture between the two clubs last October, but remains the subject of a Football Association investigation over charges that he denies.
Arsenal beat Southampton 6-1 at the Emirates Stadium.
They had three points effectively sewn up at the interval, as own goals from Jos Hooiveld and Nathaniel Clyne either side of strikes by Lukas Podolski and Gervinho handed the Gunners a commanding lead before Danny Fox pulled one back.
Gervinho and Theo Walcott - playing against his old club - netted in the second half to complete the rout as the hosts extended their unbeaten start to the season to four league games, moving up to third, a point behind United.
Champions Manchester City are level on points with Arsenal in fourth after their 1-1 draw with Stoke at the Britannia Stadium.
City have struggled away against the Potters in recent years and fell behind in the 15th minute on Saturday, as Peter Crouch - scorer of a memorable strike in this fixture last term - showing good footwork before finishing past Joe Hart.
The visitors made it 1-1 in the 35th minute as midfielder Javi Garcia, one of three players on debut for City, headed in from Carlos Tevez's cross.
Michael Owen came on to make his debut for Stoke, who were clinging on at the end as goalkeeper Asmir Begovic made a stunning save to deny Garcia and Potters captain Ryan Shawcross cleared an Edin Dzeko effort off the line.
Elsewhere, Dimitar Berbatov marked his first start and home debut for Fulham with two first-half goals, one from the penalty spot, to put them firmly in the driving seat in their home game against West Brom.
The Baggies were reduced to 10 men between Berbatov's goals when Peter Odemwingie was shown a straight red card for lashing out at Sascha Riether.
Steve Sidwell completed the Cottagers' 3-0 triumph with a follow-up strike with a minute from time, reacting when Hugo Rodallega hit the bar.
Aston Villa secured their first league win of the season, defeating Swansea 2-0 at home.
Summer signing Matthew Lowton opened his Villa account with a volley just after the quarter-hour mark and another new arrival, Christian Benteke, also got off the mark by netting in the 88th minute having been introduced as a substitute to make his debut.
In the lunchtime kick-off, Norwich and West Ham played out a 0-0 draw at Carrow Road.
The day's late kick-off saw Liverpool move out of the relegation zone as a Luis Suarez strike secured them a point at Sunderland.
Suarez netted with just under 20 minutes to go to make it 1-1 after Steven Fletcher had opened the scoring in the 29th minute, the Scotland striker's third goal in two games since joining the Black Cats from Wolves
Saturday's Barclays Premier League Results
Norwich 0-0 West Ham
Aston Villa 2-0 Swansea
Stoke 1-1 Man City
Man United 4-0 Wigan
QPR 0-0 Chelsea
Arsenal 6-1 Southampton
Fulham 3-0 West Brom
Sunderland 1-1 Liverpool