The Glassford Street camera has been producing 340 tickets a day on average to motorists who stray into its bus lane and has so far brought in £1.2million.
The device, which is one of 11 located in and around the city centre, has been responsible for one in four £60 fines handed out to errant motorists.
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Freedom of Information figures obtained by The Herald show 189,126 penalty charge notices were issued between April 1, 2012, when bus lane camera enforcement began, and October 8 this year.
Glassford Street is a one-way system with an oncoming bus lane running northwards from Argyle Street to Ingram Street. The camera accounted for 44,657, or 24%, of all the fines issued.
This was almost 20,000 more fines than the second most-abused bus lane, in Cathedral Street, which resulted in 25,298 penalties over the same period.
The £60 charge is reduced to £30 if motorists pay within two weeks.
The latest figures were revealed as five new Mk2 "supercameras", capable of catching 50 times as many motorists as standard traffic cameras, were being rolled out on the city's bus lanes.
The first one went live last Monday, weeks after Glasgow City Council set a target of raising £376,000 by 2015 through "increased bus lane camera enforcement".
Peter Rodger, of the Institute of Advanced Motorists, said the lanes on Glassford Street were poorly designed and would force motorists into bus lanes. He said: "It's quite a narrow street and there are bus stops opposite each other, so cars have to move out to get around parked buses. You'd either have to overtake the bus very tightly when there may be pedestrians, or be forced to stray out into the bus lane.
"And if you've got bus stops with 14 or 15 routes on them, as this street does, and you've got them stopping every five to 10 minutes then the road is going to be blocked about 20% of the time. It's peculiar, and poorly designed from a safety point of view."
Glasgow has received £4.3 million from bus lane fines, including £1.2m from Glassford Street. The city council says the number of fines is declining.
Stephen Flynn, of Glasgow Taxis Ltd, said: "While Glasgow Taxis' vehicles are permitted to use bus lanes, a number of our drivers have been sent charge notices for doing so on Glassford Street, which we have then had to challenge (successfully) on their behalf."
A city council spokesman said: "Regrettably, some drivers continue to break the law and, as with many other driving offences, camera enforcement is an effective deterrent. The bus lane in Glassford Street is clearly indicated through signage in the car park, at the bus lane itself and the road markings of the bus lane."