When Swit arrived in Hollywood in 1970, she performed in television shows including Gunsmoke, Mission: Impossible, Hawaii Five-O and Mannix.

Starting in 1972, Swit played the character of Major Margaret "Hot Lips" Houlihan in the television series M*A*S*H. She inherited the star-making role from the similarly large-mouthed actress Sally Kellerman, who portrayed the character in the feature film. Swit, Alan Alda, Jamie Farr and William Christopher stayed for all 11 seasons of the show, from 1972 to 1983. She along with Alda, Christopher, and Farr, all had on- and off-screen chemistry with each other, and spent a great deal of time with each other. She and Alda were the only two actors to have been on the pilot episode and the finale. She did not appear in only 11 out of the total of 251 episodes. Swit received two Emmy Awards for her work on M*A*S*H. Later, Swit was also the first M*A*S*H star to visit South Korea when she narrated the documentary Korea, the Forgotten War.