It happened at Dumfries and Galloway College in Bankend Road sometime between 10.15 pm on Tuesday and 6.45 am today, Weds.
Police officers are appealing for witnesses.
Detective Sergeant Lee Moscrop at Dumfries said: “This appears to have been a well planned break-in and the cash machine was the target for the thieves. We are asking for the help of the public to identify any suspicious activity in or around the college over the past days and weeks. It is highly possible that those responsible visited the college in order to plan this crime.
“Anyone who may have seen or heard anything which might have seemed suspicious, or even a bit unusual, should call us at Dumfries on the 101 number. Sightings of vehicle movements at unusual times or suspicious activity by anyone around the area of the college may well help us trace those responsible.”