After attending the University of Southern California, Lillis signed his first contract with the Brooklyn Dodgers in . A shortstop by trade, he spent eight years in the Dodger farm system, buried (along with many others) behind Hall of Famer Pee Wee Reese. Finally, in , the team's first season in Lillis's home city of Los Angeles, he made the major league team. But Lillis never claimed the regular shortstop job — that would go to Maury Wills — and in the middle of the campaign, he was traded to the St. Louis Cardinals. After a half season with the Redbirds, he was selected by Houston in the 1961 MLB Expansion Draft.
Lillis then spent 5½ seasons as a shortstop and utility infielder for the Astros, retiring to a coaching position in the middle of 1967. Over his ten-year MLB career, Lillis appeared in 817 games and batted .236 with three home runs. He threw and batted righthanded.
After scouting and player development posts with Houston from 1968-72, Lillis returned to the Astro coaching staff in 1973 and served under managers Leo Durocher, Preston Gomez and Bill Virdon. In August , he succeeded Virdon as manager with the club in fifth place in the National League West Division. Lillis led the team to 28 wins in 51 games and was rehired for full seasons from 1983-85. But Houston never climbed above second place, and even though Lillis compiled a winning 276-261 (.514) record during that period, Lillis was replaced by Hal Lanier at the close of the 1985 campaign.