Fillmore County Sheriff John DeGeorge said that the buggy and the Toyota SUV were travelling in the same direction along County Road 1 in Fillmore County when they collided at around 8.25am on Monday.
Two children died in the crash, while another two were taken to St Mary’s Hospital with injuries.
All four children – who are all siblings from the small rural city of Stewartville – had been travelling in the buggy.
The victims were identified as siblings Wilma Miller, seven, and Irma Miller, 11, while the survivors were named as Alan Miller, nine, and Rosie Miller, 13.
The injuries of the two surviving children are currently unclear.
The horse leading the buggy also died during the collision, KAALTV reports.
The driver of the SUV is a 35-year-old woman from Spring Valley, according to local news outlet KTTC.
No charges have been brought in the case with the investigation – led by the Fillmore County Sheriff’s Office, Mower County Sheriff’s Office and Minnesota State Patrol – still ongoing.
Minnesota State Patrol officers are planning a reconstruction of the crash to determine how it unfolded.
The tragedy comes just one week after another fatal crash involving an Amish buggy over in Alexandria, New York.
On 20 September, two children aged one and three were killed when a pickup truck drove straight into the back of the buggy.