Bobby Barnes, Fifpro's Europe president and deputy chief executive of the Professional Footballers' Association, believes collective action is now required.
He also warned the period in 2021-22, when there will be a World Cup, the Africa Cup of Nations and the Concacaf Gold Cup on top of the usual club commitments, could represent a tipping point.
"Football's governing bodies, as well as the clubs and leagues, need to get together on a global basis to try to ease this pressure," Barnes said.
"The time has come to have a holistic view. You don't play the game without the players. Their interests have to be better protected."
Research by Fifpro found that Sadio Mane, Son Heung-min and Alisson Becker were among those to have played 70 or more games over a 12-month period, including international travel in excess of 80,000km, without any mid-season break. Fifpro now wants:
●Mandatory off-season breaks of four weeks and mid-season breaks of two weeks.
●A limit on back-to-back competitive games with less than five days' recovery time.
●Consideration of annual match limits.
●An early warning system to monitor match load.
A first Premier League mid-season break takes place next month — when a round of 10 matches will be played across two weekends — but there is already fear among medical staff that it could be too little, too late ahead of the European Championships starting in June.
Barnes said the February break was "very much needed" but questioned whether the wider issues would be solved without addressing the overall annual global burden.
Newcastle manager Steve Bruce said recent injury numbers were unlike anything he had experienced.
"You get injuries by forcing players to play tired," he said. "To ask players to play four games in 10 days is ludicrous. This is the consequence."
Liverpool played nine matches in December — including two in Qatar — and manager Jurgen Klopp also believes the schedule must change.
"None of the managers have a problem with Boxing Day, but playing the 26th and 28th is a crime," he said.
Injury analyst Ben Dinnery, who runs the Premier Injuries website, described New Year's Day as "horrendous" but said that increased injuries were an inevitable consequence of extra games at this time of year.
The injuries also prompt questions of how players have been used. Jamie Vardy and Danny Ings, for example, did not start all of Leicester or Southampton's games over the festive schedule and avoided injury.
Although muscular injuries are more associated with fatigue than some of the serious knee injuries that occurred on New Year's Day, there is concern that recent workloads may have indirectly contributed.
Arsenal's Calum Chambers and Aston Villa's Wesley Moraes are set to miss the rest of the season with knee injuries. Former Arsenal and England physiotherapist Gary Lewin yesterday called on player welfare to "become a bigger factor" in scheduling.
"Common sense tells you if players are fatigued, the muscles and bones cannot react in the same way," he said.
