The annual ONS survey, which covers the 12 months to the end of March, asked people aged 16 and over across the UK to rate four areas of their personal well-being, with three of the areas - their happiness, life satisfaction and sense of the things they do in life being worthwhile - ranked on a scale from zero to 10.
The average happiness score for respondents in Burnley was 7.18 - one of the lowest scores in the UK - compared to an average UK score of 7.52. The happiest place in the UK this year was in Rushmoor in Hampshire.
According to ONS research, people's views about their health, employment, and relationship status are the factors most likely to impact how they rate their personal well-being, with bad health the most significant factor associated with reports of poor well-being, followed by being economically inactive with a long-term illness or disability.
Disability charity Scope said employers' outdated attitudes and inflexible working practices were keeping disabled people out of work.
James Taylor, head of policy at Scope, said: "This needs to change. Government and employers need to all become disability game-changers by challenging negative attitudes and tackling the many barriers disabled people face."
The ONS report noted that employment worries went beyond just having a job, and also concerned the quality of job security, wages and work-life balance.
It continued: "We know that well-being does not thrive in circumstances of great inequality. "Reducing disparities in life expectancy and health, access to skills and education, good jobs and affordable homes should be an important priority for achieving inclusive growth in all areas."
Since the survey began in 2011-12 happiness in the UK has been increasing year-on-year but has slowed in recent years. People in Burnley have also been reporting higher levels of happiness as the years go by.
This year's score was a drop from 2016-17, when happiness was at 7.82. The results for life satisfaction was also below the national average this year, although people felt more positive about how worthwhile their lives were than average.
Silvia Manclossi, head of the quality of life team at the ONS said: "An important part of our work is looking beyond the economic health of the country to how its people are faring and inequalities in society.
“Today, for the first time, we have identified how factors such as health, access to services and crime levels may affect how people rate their well-being in different parts of the UK. This can help local authorities and other organisations to better understand where services could be targeted to help improve the well-being of people in their area.”
A fourth question in the survey asks respondents to rank how anxious they felt on the previous day, with zero being 'not at all anxious' and ten being 'completely anxious'. The population in Burnley appears to have become more stressed over the last year, with anxiety levels creeping up since 2016-17.
The region coming out top in the well-being survey this year was Northern Ireland, which reported the lowest levels of anxiety and the highest levels of happiness, satisfaction and feelings of worthiness of any UK region for two years running.
The worst performing region across the board was London, while people in Wales also report lower than average satisfaction with their lives than the other nations of the UK.