NHS England medical director Professor Stephen Powis said the latest "shocking" figures, which show obesity-related admissions have risen by nearly a fifth nationally, are a growing sign that an obesity crisis is sweeping the nation.
NHS Digital data reveals that in Luton, there were 5,085 hospital admissions where obesity was a primary or secondary factor in 2019-20.
That was 2,672 in every 100,000 residents – the highest rate in the East of England, and up from the previous year's figure of 2,264. Three years earlier, the rate was 914.
Women accounted for more then seven in 10 obesity-related hospital cases in Luton in 2019-20, the figures reveal.
Nationally, there were just over 1 million admissions due to obesity in 2019-20 – up 17% from 2018-19, and equating to rate of 1,869 in every 100,000 people.
There was huge disparity in rates across England, with the most deprived areas worse affected than those with low deprivation levels.
The East of England was the eighth-worst affected of the country's nine regions, with a rate of 1,526 per 100,000 population.
The East Midlands had the highest rate last year, at 2,592 – nearly double that of the South East, which had the lowest rate of 1,382.
NHS Digital said some of the overall rise may be due to better reporting of data.
Professor Powis said the nation's "obesity crisis" is putting hundreds of thousands of people at greater risk of becoming severely ill with Covid, as well as heart attacks, stroke, cancer and other deadly diseases.
"Carrying extra pounds not only puts a strain on your physical health, but also on the health service," he added.
"As lockdown restrictions start to ease, there has never been a better time to take steps to live a healthier lifestyle."