Almost 4500 fines were handed out to motorists last year, making the route account for almost half of the ten worst locations in Scotland for speeding offences.
A total of 1883 drivers were caught near Kirkpatrick Fleming; 962 near Lockerbie; 853 near Beattock; and 743 near Ecclefechan.
And the highest speed, 125mph, was recorded at Beattock.
The figures were obtained by a Sunday newspaper from Police Scotland under freedom of information laws.
Neil Greig, the Scotland-based policy and research director of the Institute of Advanced Motorists, says that high numbers of tickets locally suggest that message is not getting through to drivers.
He said: “On the face of it speed camera activity on the M74 seems a little heavy handed as motorways are our safest roads and the M74 is one of the best in Scotland.
“However, as long as some drivers continue to flout the 70mph limit the police do need to act.
“Police Scotland must review speeding levels closely and if the mobile vans on bridges are not having a lasting impact then more high profile patrols will be needed as well.”
Roads policing inspector Neil Hewitson, based at Lockerbie, said: “The A74 Glasgow – Carlisle Road is one of the main arterial routes for traffic heading both south and north between Scotland and England and as such it carries a high volume of traffic.”