Brentford capitalised on United mistakes and were clinical in attack to score four times in 28 breathless minutes of football at the GTech Community Stadium to send their home fans into raptures.
For Manchester United, this only compounds matters after last week's 2-1 home defeat to Brighton & Hove Albion, which leaves them bottom of the table.
United's seventh successive away league defeat was assured long before the interval as Brentford took ruthless advantage of a catalogue of errors by the visitors.
It was the first time since 1960 that United have conceded at least six goals in their first two matches of a top-flight season and the first time they have lost their opening two matches since 1992 when they went on to win the title.
Erik ten Hag is also the first Manchester United manager to lose his first two games in charge since John Chapman in 1921.
"It's easy to dismantle this United side, just be organised and fight and you're there," said former United player and Sky Sports pundit Neville.
"They (United) are absolutely drained of all confidence. They are struggling badly and they have been now for 12 months... But, today was a new low and it seems continually that Manchester United can pass their previous lows and when is the lowest low going to come? Because the reality of it is is this is really, really bad."
His fellow pundit, Jamie Redknapp added: "From the (United) players that started and finished that game, I don't think I have ever seen such an abject performance from a club that I would regard as one of the biggest in the world."
For Brentford, whose starting line-up cost in the region of 55 million compared to the more than 400 million of United's, have picked up four points in their first two games.
"It was just hard work. We knew the high press would affect them. It was clear to see that if you work hard, you get the result," Toney told Sky Sports.
"We know they have great talent in there and have some players who can change the game. When you work like we did today and run all over them, you get a result like we did."
United has Cristiano Ronaldo back in their starting line-up but the Portuguese forward barely got a look in.
The confidence drained out of United from the moment David de Gea allowed Josh Dasilva's shot to end up in the back of the net in the 10th minute.
Eriksen, who got a mixed reception from Brentford's fans, then inadvertently gifted his former club their second as United looked shellshocked by the energy of their hosts who went on to record their biggest top-flight victory since 1938.
Things will not get any easier for United whose next game is against Liverpool.
"It was a horrible day," De Gea said. "I should have saved the first shot and then the result may have been different.
"Other teams concede one goal and win 5-1. We have to react much better. It was a poor performance."