She was joined by Phil Jones, the chairman of NHS Dumfries and Galloway, to cut the turf on the site at the western edge of the town.
The multi-million pound complex will house 350 beds, a heli-pad and 980 parking spaces.
MSP Ms Robison also opened Melrose Ambulance Station earlier in the day.
"It is going to be a fantastic new facility for the people of Dumfries and Galloway in 2017 when the hospital is completed," she said about the Dumfries site.
"It is absolutely essential that we make sure that the health facilities in Scotland are fit for the 21st Century."
She rejected criticism of the single-room set-up planned to be used in the hospital.
"I think the most important thing here is patient care and patient safety," she said.
"When you look at the elements of infection control there is absolutely no doubt there are huge benefits to having single rooms."
Ms Robison cited the example of a norovirus outbreak needing a whole ward to be closed rather than a single room.
"It has real benefits and I think people once they get in and start using the new hospital in a couple of years time will see the benefits and appreciate those," she said.
She added that there were also economic benefits attached to the project.
Ms Robison said there would be 150 new jobs as well as 36 new apprenticeships during the construction phase, which she said was a "great story for Dumfries and Galloway".
The new Â£2.9m ambulance facility has been built next to the Borders General Hospital.
"I am very impressed indeed it is a first class, state of the art facility which is great for staff and great for patients because of the added benefits of quicker response times," Ms Robison said at the ambulance station opening.
"The co-location with Borders General Hospital I think is important as well.
"This is a part of our investment in the NHS across Scotland and it is good to see the Borders getting part of that investment."
Scottish Health Secretary Shona Robison has marked the official start of building work for the new Dumfries hospital at a ground-breaking ceremony.