Glengarry Castle Hotel, which lies on the shores of Loch Oich, was targeted on Monday night when it was closed to guests over winter.
The intruders managed to make off with the paintings without alerting the hotel caretaker, who was the only person in the building at the time.
The haul included two by works by Victorian artist George Armfield.
Hotel manager Donald MacCallum, whose family has owned the estate - which includes the famous Invergarry Castle, where Bonnie Prince Charlie sought solace after his defeat at Culloden - for half a century, said he was devastated at the loss.
Mr MacCallum added: "The thieves took a total of four of our collection of oil paintings. These four are valued at around £35,000.
"Two of them by George Armfield were very large, four foot by three foot. These were placed above the fireplace in the lounge and library and attracted a lot of attention from guests.
"These main ones were of hunting scenes. One showed a grouse that had been shot with dogs jumping around it. The other showed three dogs around a table looking guilty as they had obviously pulled some dead grouse off it.
"They were impressive paintings and very fitting for this house. They will be very much missed."
Of the other smaller paintings, one was by an artist called William Kennedy and showed a scene of a man ploughing fields.
Mr MacCallum said it would have taken at least two thieves to have carried off the larger works.
He added: "We are closed between November and March, so there was only a handyman living in the hotel at the time.
"We live a few hundred yards away in the grounds, so saw and heard nothing."
Northern Constabulary detectives have appealed for information about the theft.