While attending the university, Simmons competed in fencing and swimming and also acted in a few theater productions. Simmons left the Twin Cities in the 1930s to launch his film acting career in 1937. He soon became an MGM contract player. Many of his minor movie roles went uncredited through the 1940s. One even included his portrayal of a Mountie in King of the Royal Mounted produced by Republic Pictures. Starting in 1943, he began appearing in credited roles, beginning with his appearance in The Youngest Profession, starring Virginia Weidler. From 1943 through 1949, he would appear in seventeen films, of which ten listed him in the credits.

The 1950s mirrored the 1940s, with him appearing in several films and television series, at times uncredited. In 1952 he played the co-pilot in Above and Beyond. In 1955, Simmons won his best-known role, portraying Sergeant william Preston in Sergeant Preston of the Yukon. Following the end of the series in 1958, he continued to have a successful acting career, mostly in television series guest appearances, through 1982, with his last role being in CHiPs, guest-starring along with Sue Lyon and Cesar Romero.

In 1967, Simmons was cast as Meriwether Lewis, with Victoria Vetri as Sacajawea in the episode "The Girl Who Walked the West" of Death Valley Days, hosted by Robert Taylor. Don Matheson portrayed william Clark, and Victor French was cast as Charbonneau. In 1969, Simmons played W. Frank Stewart, a silver mining operator who served from 1876 to 1880 as a Nevada state senator, in the Death Valley Days episode "How to Beat a Badman". In the story line, Stewart is determined to gain at a bargain price a silver claim being worked by two young former outlaws, played by Tom Heaton and Scott Graham.

On January 11, 2003, Simmons died (with a diagnosis of Alzheimer's disease) in Oceanside, California at the age of 89.