Professor Sir Mike Richards said the NHS "stands on a burning platform" following the first round of new inspections of the nation's hospitals.
The Care Quality Commission's (CQC) chief inspector of hospitals said it has become clear the model of acute hospital care which once worked well for the NHS "cannot continue to meet the needs of today's population".
He said there is a "wide variation in quality" between hospitals and between services within the same hospital, following the first round of comprehensive inspections of England's 136 acute non-specialist trusts and all 18 specialist trusts.
Inspectors uncovered pockets of "very poor quality care" in good hospitals, he added.
He said the scale of the challenge is "unprecedented".
Sir Mike said rising demand for care and economic pressures are creating "difficult-to-manage situations that are putting patient care at risk".
The CQC's State of Hospitals report says: "The safety of hospitals remains our biggest concern, with four out of five trusts needing to improve."
Sir Mike criticised a "failure to learn" when things go wrong.
Overall 81% of the 136 non-specialist trusts were deemed to be inadequate or to require improvement for safety.
Some 11% of hospital trusts were given the lowest rating for safety.
None received a rating of outstanding in this area.
The authors of the report said some trusts have "blind spots" about the quality of care they are delivering.
More than half of specialist trusts (53%) were rated as requiring improvement in terms of safety.
The authors of the report wrote: "We are also concerned that some may be over-reliant on their reputation and not assuring themselves of the quality of care they are delivering."
Across 199 urgent and emergency services inspected, 7% were deemed to be inadequate.
Urgent and emergency services and medical care had more ratings of inadequate and requires improvement than good or outstanding, the report said.
The CQC said the proportion of urgent and emergency services rated inadequate reflects that many A&E services are struggling to cope with increasing numbers of patients.
The regulator introduced a new inspection programme in 2013 following the publication of the public inquiry report into the care scandal at Mid Staffordshire NHS Foundation Trust.
It has inspected all NHS acute and specialist hospital trusts under the new regime.
The latest report, which brings together all the inspections, highlights areas for concern but also praises improvements and celebrates outstanding care.
NHS staff have been applauded for their caring attitudes to patients, and the report shows no hospital trust has been given the lowest rating for providing a caring atmosphere for patients.
"Frontline staff are the heroes of our reports," the authors wrote. "We have found high levels of compassionate care in virtually every hospital."
Sir Mike said: "We have witnessed some fantastic care and examples of innovative practice, but we have also found a wide variation in quality both between hospitals and between services within the same hospital.
"Safety remains a real concern, often due to a failure to learn when things go wrong.
"Strong leadership that instils a culture of learning and an environment where staff are listened to can play a vital part in bringing about improvements.
"Overwhelmingly, we see staff behaving in a caring way, which is supported by what we hear from patients. The unwavering dedication and commitment of staff shines out from our inspection reports.
"What is clear is that while staff continue to work hard to deliver good care, the model of acute care that once worked well cannot continue to meet the needs of today's population.
"The NHS now stands on a burning platform - the need for change is clear, but finding the resources and energy to deliver that change while simultaneously providing safe patient care can seem almost impossible.
"What this report demonstrates, however, is that transformational change is possible, even in the most challenging of circumstances - we have witnessed it, and seen the evidence that making practical changes to the way that care is delivered can benefit patients."
His foreword to the report adds: "The scale of the challenge that hospitals are now facing is unprecedented - rising demand coupled with economic pressures are creating difficult-to-manage situations that are putting patient care at risk."
An NHS England spokesman said: "CQC are right to praise dedicated NHS staff for delivering great care under pressure, and they are also right to argue for the more profound changes now being planned in how acute hospital care is delivered across England."