Premier League chief executive Richard Masters says it is "absolutely critical" that fans are allowed back inside stadiums as soon as possible.
He says failure to do so will cost clubs £700m during the 2020-21 season, which starts on Saturday.
Football has been played behind closed doors since its return in June following the coronavirus lockdown.
As it stands, no fans will be admitted to top-flight matches in England before October at the earliest.
Speaking later on Wednesday, Prime Minister Boris Johnson announced there will be a "review" of plans to bring fans back into stadiums from 1 October in England, amid growing numbers of positive Covid-19 cases.
Masters told BBC Sport that matches behind closed doors "can't go on forever", as clubs have already lost more than half a billion pounds from the disruption to the final quarter of last season.
"We have to get back to fans inside stadia as quickly as possible - that's the big thing that's missing, economic or otherwise - we need fans back inside stadiums for all sorts of reasons and it's the number one priority," he said.
Masters also revealed he was still hopeful some fans could return to grounds next month, despite the rising number of cases of coronavirus in the UK and the government's new restriction on gatherings of more than six people, which comes into effect on Monday.
He admitted clubs "would have to adapt" because "there will be bumps in the road".
"It doesn't lower our ambitions - it just means that we'll have to adapt - it's one thing we've shown over recent months, we're able to adapt to the situation," Masters said.
"We wait to see what impact it has on the government's testing programme, and permissions it's going to give, and also on that crucial 1 October date. We wait to see what the government decides and we'll remain in dialogue with them throughout.
"We always knew September was going to be a difficult month at the start of the return to normality the government was talking about, and so we should anticipate bumps in the road."
Premier League's key targets
Masters said the Premier League has three main objectives - the "big challenge" of ensuring 380 matches finish on time this season, getting fans back into full stadia, and returning the Premier League economy to full health.
Premier League revenue was down £700m in the final quarter of last season.
"It's not just the loss of matchday revenue," he said. "Every Premier League match on average generates about £20m for the economy both local and national so we want to play our part in helping the economy to recover as well.
"I think perhaps there is a perception the Premier League economy can withstand just about anything, but if you do lose £700m out of a planned budget it's going to affect things and clubs have had to make some very difficult decisions.
"That is why it is important we focus on those three key objectives and obviously everyone hopes that from next season we can return to full normality, but it's a huge challenge going forward.
"Financial issues are very real, they're there, economic uncertainty is in front of us, and we just have to have a clear plan and stick to it."
'Confidence' that season can be finished if another wave hits
The 2019-20 Premier League season was suspended in March as a result of the coronavirus pandemic and restarted on 17 June, exactly 100 days later.
In last week's Premier League meeting, there was a commitment to complete this coming season should a second wave of coronavirus hit England, although a final decision is yet to be made.
Players and staff will now be tested once a week rather than twice.
"What we were able to create was a very safe environment, a very low prevalence of positive tests around a short campaign of 92 games," said Masters about the end of last season.
"It does give us the confidence that that formula can continue to work.
"You can never rule it out, we have to be cautious, and everyone has to play their part.
"But it must build confidence that we can get our season away and get it finished on time."
'Difficult decision' to terminate China streaming deal
Earlier in September, the Premier League terminated its £564m contract with its Chinese licensee with immediate effect.
BBC Sport was told streaming service PPTV withheld its latest payment of £160m, due in March.
"It was a very difficult decision," said Masters. "PPTV have been a very good partner for us.
"We had some contractual dispute with them that we couldn't resolve so we took the very difficult decision, the commercial decision, to move on and to find a new way of doing things in China."
China was the English top flight's most lucrative overseas television rights territory, with a three-season deal agreed in 2019.
"We hope to resolve the issue as soon as we can," Masters added. "I want to make the best decision rather than the quickest decision, we know that there is a lot of demand to see Premier League matches out there, clubs have got millions of supporters who want to see their matches and so we hope to deliver something as soon as we can.
"There are all sorts of things to take into account, reach and value are two of them, but I think really it's about choosing the right path forward in a very big market, a crucial market to the Premier League."
'Sympathy' for Newcastle fans
Masters also spoke to BBC Sport about the collapse of the potential takeover of Newcastle United in June, saying he had "sympathy" for Magpies fans because of the lack of information they received.
A Saudi Arabian-backed consortium ended its £300m bid to buy the club off Mike Ashley in July, after the group rejected the Premier League's offer of arbitration to determine who would own the club.
The deal was still being scrutinised under the Premier League's owners' and directors' test.
"I think there is a reasonable expectation on all the parties involved for confidentiality, I think that's what we were trying to respect," said Masters.
"We've been as transparent as we possibly can and had, albeit brief, discussions with the Newcastle United Supporters Trust where I've answered their questions and written an letter to local MPs explaining as much as I can about the process and some of the issues we faced, and so hopefully we have been more transparent.
"Obviously what we can't talk about it what might happen in the future.
"We are going to look again at the owners' and directors' test and some of the issues and specifics of it.
"It's time to have another look at it in light of recent events."