That is close to double the average wage in La Liga, which is just more than $2.1m per player per year, or $43,900 a week.
And United are now the fourth best-paid team in world sport and the best-paid football team in the world, man for man.
The global sports salary survey (GSSS) found the average first-team wage at Old Trafford equates to basic pay of $196,534 a week. The acquisition of world-record signing Paul Pogba and high-earner Zlatan Ibrahimovic have propelled them up the list.
Barcelona, home to Lionel Messi, Neymar and Luis Suarez, are the second best-paid football team and fifth across all teams, averaging $9.92m per player a year, or $193,059 a week, while Manchester City are third ($9.56m per year, $184,203 per week), and ranked No 9 in the world. Real Madrid are the fourth best-paid football team, the No 19 team across all sport.
The survey shows how the NBA teams have collectively stretched their lead to keep American basketball as clearly the world's best paying sport. The 449 players on the rosters of the NBA's 30 teams earn an average $8.5m a year.
The Premier League's financial strength in depth is mightier than ever thanks to new TV deals now in force for the 2016-19 seasons, when Sky and BT Sport will pay $9 billion between them for domestic live rights.
Foreign broadcasters will pay $5.3 billion for overseas rights collectively, and Match of the Day and other programmes will contribute hundreds of millions more for highlights and delayed rights.
The Premier League's central earnings, the vast majority from TV, will be $5.3 billion a year for the next three seasons, and the majority of that will go to clubs, where the biggest single outlay is player wages.
Women Still Lag Behind in the Pay League
The gender equality gap in sport is put in stark relief by the new figures on pay.
For example, the combined salaries of every player in the 2016 season in the women's basketball competition in America, the WNBA, which is the highest paying women's league in the world, was about $15.4m.
There are 95 players in the 2016-17 men's NBA who are each earning more than the entire WNBA.
The Premier League's clubs flexed their financial muscle in dramatic fashion over the summer when, led by Manchester's two teams, they smashed the single division spending record for one transfer window by spending almost $2.1 billion.
United spent $257m on stars for new manager Jose Mourinho, breaking the world record to sign Pogba for $158m as well as hiring Henrikh Mkhitaryan, Eric Bailly and Ibrahimovic. Pogba, Rooney and Ibrahimovic all feature among the top 10 best-paid players in the world.
City spent $298m this summer on the likes of John Stones for $84m, Leroy Sane for $66m and Ilkay Gundogan for $35m, and have three of the world's top 20 best-paid players in Sergio Aguero, Yaya Toure and Kevin De Bruyne.
United's first-team squad cost $925m to assemble - more than any club in the world - ahead of Real Madrid in second place ($909m) and City in third ($805m). The biggest spenders on fees are the same cohort of super rich clubs who lead the way in wage expenditure. Barcelona's squad cost 'only' $586m to assemble because some of their key talent, Messi included, were produced by the club's academy.
Celtic have the biggest average first-team salary in Scotland at $1,271,714 per player, more than double the next biggest at Rangers ($561,467 per year).
Salaries peaked at Celtic four years ago at an average of just over $1.77m a year but wage bills in Scotland buck the general trend and are down.
The survey compares average basic pay in leagues ranging from the NBA, NFL, NHL hockey, MLB baseball and MLS in the USA, to football leagues in Europe and Asia, and an assortment of other popular leagues covering Australian Rules football and IPL cricket.
Premier League average pay has multiplied by almost 32 times in 25 seasons, from about $136,381 in 1992-93 to $4.25m now. United's first-team salaries have grown from about $247,966 per year in 1992-93 to more than 40 times as much.
