Around 40% of working households cannot afford an average-priced two- or three-bedroom home with an 80% loan-to-value mortgage, data from Zoopla shows.
It adds that 74% of workers living in London are unable to afford to buy an average-priced two or three bed home.
And 58% are unable to buy across southern England – the South East, South West and East of England.
The survey says higher house prices make homeownership “a major challenge for workers across southern England, more so than the rest of Britain”.
Across the rest of the UK, “access to homeownership is better” but the study finds that 20% to 30% of workers on the lowest incomes are unable to buy.
The study also finds that home affordability is becoming a challenge across a growing number of regional cities outside southern England, as rising employment and incomes in these areas have driven house prices and rents higher.
In York, 61% of workers are unable to buy a two or three-bed home, followed by 57% in Trafford, Greater Manchester, 46% in Leicester and 45% in Edinburgh.
In total, there are 18 local authorities outside of southern England where more than 40% of workers are unable to buy.
The report adds that high house prices have “compounded pressure” on the private rented sector where the total number of rented homes has been broadly static since 2016.
The study finds that, at a national level, just 27% of full-time workers are unable to afford private rental costs compared to a higher level of 40% for buying.
Renting is most unaffordable in London where 67% of workers living in London can’t afford the rent for two or three-bed homes, with 32% of workers unable to afford rent across southern England.
Propertymark chief executive Nathan Emerson says: “Regional house price differences remain a significant concern for people looking to purchase a property.
“For many people, owning a home is becoming a very challenging prospect to achieve.
“All eyes will likely be on the forthcoming budget to see what proposals may affect those looking to purchase, but also to see if what support might be offered to first-time buyers.
Zoopla executive director Richard Donnell points out: “Our analysis has important implications for the type and tenure of homes that need to be built over the next five years.
“The narrative on home building needs to move beyond headline numbers and focus on the types and tenures of new homes that are needed to support economic growth and improve access to home ownership.
“There is no simple one-size-fits-all approach, the types of homes that are needed vary across the country.
“Increasing the number of social and private rented homes that are built is a key pillar in easing pressures across the housing market.”