Around 120 vehicles were stopped across Gloucestershire over the weekend - with a fine issued for one car travelling from Manchester to Bristol.
Police stopped those on main routes to ask why they were travelling - but say it was the quietest the M5 has ever been.
They say the vast majority had a good reason for being out, but one vehicle was on the M5 travelling from Manchester to Bristol to collect a car that had been bought.
The group was issued with £60 fines, and other forces were also told in case they are caught breaking lockdown restrictions again.
Inspector Dan Wakeford said: “Our approach has been that officers will engage with motorists to establish why they are travelling, explain the risks to public health, encourage people to consider if they need to travel and then consider enforcement when people have refused to take the advice on board.
“Our teams have been polite but inquisitive, alert and sensitive to other potential reasons why people may be travelling. Where appropriate we have asked for letters explaining that the person is a key worker and people have been happy for us to do this.
“The one example of non-compliance shouldn’t overshadow the fact that this was one of the quietest days on the M5 in history and most people do get it.
“However it is our first enforcement action and should demonstrate that we will use our powers where needed.
“Please continue to act responsibly as my officers will be out on major routes again today and in the week ahead.
"And with next weekend being the Easter weekend please remember you should not be travelling anywhere to go on holiday."