Ramis died early Monday morning at his Chicago-area home, surrounded by family and friends, according to a statement from his Los Angeles representatives, United Talent Agency.
Ramis died of complications from autoimmune inflammatory vasculitis, a condition he had battled for the past four years.
Chicago-born Ramis started his comedy career in his hometown's influential Second City improv comedy theatre in 1969, where he would encounter his friends and regular collaborators such as John Belushi, Bill Murray and Dan Aykroyd.
When the troupe launched its landmark television series SCTV in the late 1970s, Ramis was its first head writer, as well as one of the cast members.
Nearly a decade later, he broke through into Hollywood with the blockbuster comedy National Lampoon's Animal House, starring Belushi, and became known for some of the most popular comedy films of the 1980s.
Through his career, he would mix screenwriting, directing, producing and acting roles. His best-loved titles include his role in the Ghostbusters films — in which he portrayed the straight-laced Dr. Egon Spengler — and directing the comedy classic Groundhog Day, starring Murray.
He often teamed with his former Second City colleagues for wild and silly films, includingStripes, Caddyshack, Meatballs and National Lampoon's Vacation.
In recent years, his work included directing episodes of The Office, the film Year One and cameo roles in movies by comedy filmmakers he'd inspired (including Judd Apatow's Knocked Up).
He is survived by his wife, Erica Mann Ramis, his children Julian, Daniel and Violet and two grandchildren.