It also showed women in Wales were 40% more likely to be classified physically inactive than men.
The charity said lack of exercise significantly increased risk of coronary heart disease and early death.
The Welsh Government said it was working to increase opportunities to make physical activity part of everyone's daily routine.
Dr Mike Knapton, associate medical director at the British Heart Foundation (BHF), said levels of physical inactivity in the UK remained "stubbornly high".
The charity's Physical Inactivity and Sedentary Behaviour Report showed the north west of England had the highest percentage of inactive adults - 47% - and the south east of England had the lowest - 34%.
In Wales, 42% of adults were classed as inactive.
The report defined "inactive" as not achieving the government guidelines for physical activity of 150 minutes of moderate exercise a week and strength activities on at least two days a week.
The report also showed physical inactivity was high among people who have gone on to suffer a cardiac event.
More than eight in 10 people in Wales, when referred for cardiac rehabilitation after suffering a heart attack or undergoing heart surgery, failed to meet the government's exercise recommendations, it said.
The charity released the report as it launched its MyMarathon challenge in a bid to boost the nation's physical activity.
The challenge encourages people of all fitness levels to run the 26.2 miles in their own time over a month, from as little as a mile a day.
Dr Knapton said: "Physical inactivity is one of the most significant global health crises of the moment.
"Making physical activity easier and more accessible for all is of paramount importance if we are to reduce the burden of inactivity-related ill health."
The BHF said evidence showed keeping physically active can reduce the risk of heart and circulatory disease by as much as 35% and risk of early death by as much as 30%.
A Welsh Government spokesman said: "We recognise the importance of being physically active and the health impact of sedentary lifestyles is a cause of concern globally, not just in Wales.
"We are working across government, and with a range of partners, to increase opportunities to make physical activity part of everyone's daily routine through a range of legislation, policy and programmes.
"We will be publishing a cross-cutting Healthy and Active strategy shortly."
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