In March 1943, Grigas reported in Boston for induction into the Army, but he was rejected due to an undisclosed ailment. Grigas instead opted to play professional football after being selected by the Chicago Cardinals in the second round, 14th overall pick, of the 1943 NFL Draft. During the 1943 season, Grigas appeared in all 10 games, principally as a fullback, for a Chicago Cardinals team that compiled a winless 0–10 record. In his rookie season, he was the Cardinals leading rusher and gained 558 yards from scrimmage, 333 rushing yards, and 225 receiving yards. During the 1944 season, Grigas appeared in nine games for the Card-Pitt, a team that compiled a winless 0–10 record. Grigas ranked first in the NFL with 1,154 all-purpose yards and 471 kickoff return yards, second with 1,300 yards of total offense and 610 rushing yards, and eighth with 690 passing yards. On November 12, 1944, he outgained the entire Detroit Lions team 123 rushing yards to 78 and 177 passing yards to 41, but the Lions still won, 21–7. At the end of the 1944 season, Grigas was selected as a first-team All-NFL player by the International News Service and as a second-team All-NFL player by the United Press International. He was also one of six players to receive votes in balloting for the NFL Most Valuable Player Award. Grigas could have accumulated even more impressive statistics in 1944, but he quit the team before the final game, leaving the team with a letter citing his mental exhaustion at playing with a team that had gone 0–9 in the first nine games. Grigas wrote:
"My action, for what I just did, may not be the best in regard to good, ethical business. Think what you may of me, but I sincerely believe that in all justice it is for the best. I had that desire which you so often mentioned in your lectures, but how long a person can have any desire depends on the frame of mind under which he plays. The human mind is the faculty of the soul, which is influenced by the human body. When your mind is changed because of the physical beating, week in and week out, your soul isn't in the game.... I tried to stick it out, but it has reached the stage where the mind is stronger than the will."
Chicago coach Phil Handler later explained Grigas decision as follows:
"He worked days in a steel mill at a job where he had to stand all the time. The team practiced at night and because of a shortage of backs Grigas had to work out both on offense and defense. Then Sundays he played sixty-minute football. The strain was too great, and he finally gave up."
In early September 1945, the Boston Yanks acquired Grigas from the Cardinals in exchange for reserve list players and cash. During the 1945 season, Grigas appeared in all 10 games for the Yanks and totaled only 160 rushing yards on 64 carries for an average of 2.5 yards per carry. In 1946, Grigas rebounded with 426 rushing yards on 84 carries for an average of 5.2 yards per carry. In his final NFL season, Grigas gained only 52 rushing yards on 27 carries for Boston, missing part of the season with injuries. In January 1948, Grigas was traded by Boston to the Detroit Lions in exchange for quarterback Roy Zimmerman. However, he did not appear in any regular season NFL games after the 1947 season.