After signing, Smalley was sent to the Pittsfield Rangers in the AA Eastern League where he held his own, hitting .251 with 14 home runs and 42 RBI as a 21 year old straight out of college. Following a brief stint with the AAA Spokane Indians, Smalley would be promoted to the big leagues for good, seeing time in 78 games for the Rangers in 1975, despite hitting only .228 with 3 home runs. Smalley would start the 1976 season back in Texas, but would not improve on his 1975 average. On June 1, his career would take a major corner.
Under the ownership tenure of Calvin Griffith, the Twins franchise made few headlines in the transaction department. However, Smalley's arrival to, and departure from, the Twins both involved blockbuster trades. On June 1, 1976, Smalley was traded to the Twins, along with Texas infielder Mike Cubbage, pitchers Jim Gideon and Bill Singer and cash, for Twins' ace Bert Blyleven and shortstop Danny Thompson. Smalley would be inserted into the Twins' starting lineup and man shortstop until 1982. During his first go around with the Twins, Smalley would develop into an all-star.
Smalley's best season came in 1979, when he was voted the starting shortstop for the American League in the All-Star game. Smalley had a sensational first half of the season, entering the break with the second-highest batting average in the Major Leagues (.341). Though he tailed off in the second half, Roy established career highs in runs, RBIs and home runs, and was named the shortstop on The Sporting News AL All-Star team. In 1979 he also led the league in games played, plate appearances, all fielders in assists, and all shortstops in putouts, while hitting .271 and leading the team with 24 home runs and 95 RBI. He did not build on this season with the Twins, as injuries struck, and he played only 133 games in 1980 and 56 in 1981.
After showing that he'd recovered from his injuries, Smalley was traded on April 10, 1982 to the Yankees for pitchers Ron Davis and Paul Boris and shortstop Greg Gagne. With the Yankees, Smalley showed a glimpse of the player he had been in 1979, hitting 20 home runs in 1982 and 18 in 1983. After a bad start to the 1984 season, in which he hit only .239 with 7 home runs and 26 RBI over the first 67 games of the season, Smalley was traded again, this time to the White Sox for middle reliever Kevin Hickey and future Pittsburgh Pirates Cy Young and 155-game winner Doug Drabek.