United dethrone Real Madrid – who held top spot for 11 years – after accumulating a record revenue of 689m euros (£515m) during the 2015-16 term.
The Premier League club saw commercial revenue grow by 100m euros (£71m).
Combined revenue for the top 20 clubs during the 2015-16 season grew 12% to 7.4bn euros (£6.41bn) – a new record.
It is the first time Manchester United have topped the annual Deloitte Football Money League since the 2003-04 season.
Real drop down to third, behind Spanish rivals Barcelona, who remain in second spot.
German giants Bayern Munich move up a position to fourth and Manchester City also climb a spot to fifth – having generated 524.9 euros (£392.6m) – up from 463.5 euros (£352.6m) during the previous season.
It is the first time they have reached the top five of the annual list.
Eight Premier League clubs make the top 20, with revenues totalling nearly 3.2bn euros (£2.4bn).
Champions Leicester City (20th) enter the top 20 for the first time. They produced a revenue of 172m euros (£128m) – which is almost five times the revenue generated two seasons before in 2013-14.
Arsenal, Chelsea, Liverpool and Tottenham remain in seventh, eighth, ninth and 12th place, with West Ham in 18th position.
Dan Jones, partner in the Sports Business Group at Deloitte, said Manchester United’s record revenues were achieved by “phenomenal commercial revenue growth”.
He added: “In recent years, their ability to secure commercial partnerships with value in excess of that achievable by their peers has been the crucial factor in enabling the club to regain their place at the top of the money league.
“That said, they’ll face strong competition from Barcelona and Real Madrid to retain the top spot in next year’s edition, due to the lack of Champions League football, the weakening of the pound against the euro and, over the longer term, as other clubs enter the commercial market demanding similar deals, using United as the precedent.”
|Deloitte Money League Table 2015-16 season – the top 10|
|Teams (positions last season)||Revenue in €m (£m in brackets) 2015-16||Revenue 2014-15|
|1 (3) Manchester United||689 (515.3)||519.5 (395.2)|
|2 (2) Barcelona||620.2 (463.8)||560.8 (426.6)|
|3 (1) Real Madrid||620.1 (463.8)||577 (439)|
|4 (5) Bayern Munich||592 (442.7)||474 (360.6)|
|5 (6) Manchester City||524.9 (392.6)||463.5 (352.6)|
|6 (4) Paris St-Germain||520.9 (389.6)||480.8 (365.8)|
|7 (7) Arsenal||468.5 (350.4)||435.5 (331.3)|
|8 (8) Chelsea||447.4 (334.6)||420 (319.5)|
|9 (9) Liverpool||403.8 (302)||391.8 (298.1)|
|10 (10) Juventus||341.1 (255.1)||323.9 (246.4)|