MacIsaac is a surname. Notable people with the surname include:
Angus MacIsaac (born 1943), English educator and businessman
Angus MacIsaac (footballer) (1900-1944) Australian rules footballer
Ashley MacIsaac (born 1975), Canadian fiddler
Dave MacIsaac (born 1955), Canadian musician
Martha MacIsaac (born 1984), Canadian actress
Rob MacIsaac (born 1962), Canadian politician