St. Louis-born Dave was signed by the Orioles in 1958, raking in a huge bonus of $100,000. He made it to the bigs after posting an eye-popping .298-35 HR-114 RBI line for the Aberdeen (SD) Pheasants in his second pro season. He had difficulty translating those numbers to the American League, batting .186 and .173 in his two years in Baltimore (1960 and 1962, with another full season in the minors in between). He would strike out once every 2.48 times at-bat for his career, an unprecedented rate. Some of his offensive shortcomings were assuaged by a willingness to take a base on balls; with the O's he had almost as many walks as hits (47/51)! Nicholson also showed flashes of power, totaling 14 longballs in less than 300 at-bats. That included three homers in a two-day span in May of 1962.
In January 1963, Dave was part of a big trade, heading to Chicago with Ron Hansen, Pete Ward, and Hall of Famer Hoyt Wilhelm in exchange for Al "Fuzzy" Smith and another Hall of Famer, shortstop Luis Aparicio. Given a regular position as the starting left fielder, Nicholson reached his peak as a major leaguer, slugging a team-best 22 home runs, driving in 70, and walking 63 times. Of course he still posted a low average (.229) and led the A.L. in strikeouts with a then-record 175. Curiously, he also hit half as many doubles (11) as homers. In 1964, he would drop to .204 with 13 HR and 39 RBI while playing 97 games. One of the brighter moments of that year saw him reach the roof of old Comiskey Park with a home run, though. His 126 whiffs were fifth-highest in the league. After an incredibly poor 1965 (.153 in 85 AB) Dave waved bye-bye to the Windy City.
It was on to Houston in 1965, where the big-swinging righty regained his footing as part of a right-field platoon. He batted a career-best .246 with the Astros, and 22 of his 69 hits went for extra bases. In the offseason, he was dealt to Atlanta in the trade that ended Eddie Mathews' fifteen-year tenure with the Braves. He wouldn't return from the minor leagues until September, and his last taste of major league action saw him go 5-for-25 with no extra-base hits.