Dryden played his Junior A hockey in Toronto, spending two years with the St. Michael's Majors and winning the Memorial Cup in 1960-61 before playing a year with the Toronto Marlboros in 1961-62.

As the older brother of a hockey legend, Dave Dryden played much of his professional hockey career in the shadow of his younger, bigger brother Ken. Dave was 24 before he got his first opportunity to play in the NHL when the Chicago Blackhawks called him up from the minors in 1965-66 for eleven games. With the advent of expansion two years later, it opened the door of opportunity for many players, including the likes of Dryden, who played in 27 games for the Blackhawks in 1967-68. Despite posting only a 7-8-5 record, with a 3.03 GAA, he sufficiently impressed enough people in the league that he ensured himself a position, if not with the Hawks, then certainly elsewhere. In 1968-69, he played in 30 games for Chicago, but was deemed expendable with the arrival of Tony Esposito.

The expansion Buffalo Sabres took Dryden and he was immediately put to use, playing in ten games in 1970-71. The following year he started in 20 games for the Sabres, relieving starter Roger Crozier from time to time. His workload was increased to 37 games the next year, with he and Crozier effectively shared the workload. Illness sidelined Crozier for much of the 1973-74 campaign, which left Dryden tending goal for 53 games with Buffalo, by far his busiest NHL season ever. He had a record of 23-20-8 with a 2.97 GAA. It was the perfect year to showcase his talents, and with his stock at a high, he opted to pursue his opportunities in the WHA, where he signed with the Chicago Cougars.

Dryden spent the last five years of his professional career in Edmonton, playing with the Oilers. At the age of 37, he had by far his finest pro season, playing in 63 games, winning 41, losing just 17 and tying two. He posted a strong 2.89 GAA and three shutouts while being named to the WHA's MVP and receiving the Gordie Howe Trophy. He was also given the Ben Hatskin Trophy which went to the best goalie in the league and was named the First Team all-star goaltender. Dryden remained with the club for its first year in the NHL in 1979-80 before retiring at the age of 38 and served as a playing associate coach that season.

He coached the Peterborough Petes for two years in the early 1980s and served as the goaltending coach for the Detroit Red Wings in 1983-84. During his tenure in Peterborough, Dryden was suspended along with Oshawa coach Bill Laforge for their part in a huge on-ice brawl which ended up with both coaches involved in a melee requiring the police to be called in to break up the disturbance.

The most memorable moment for Dave Dryden came when he and Ken played against each other for the first time, on March 20, 1971. The historic event almost did not take place, though. Prior to the game, Buffalo GM Punch Imlach announced Dave Dryden would be starting in goal for the Sabres, looking to hype the game against Montreal, clearing assuming that brother Ken would be tending goal for the Canadiens. However, the Habs threw a wrench in the plans, starting Rogie Vachon. To counter what he perceived as silly antics by the Canadiens, Imlach responded in kind by replacing Dave Dryden with backup Joe Daley. But, as fate would have it, Vachon was injured in the second period and Ken Dryden took over in the Montreal crease. Imlach, always thinking of promotion for the game, immediately pulled Daley and sent Dave Dryden out for the Sabres to the delight of the crowd.

Montreal won the game but the crowd will never forget how the two brothers met at center ice after the game and embraced. It was the first and only time in NHL history that two brothers faced off against one another in opposite goals.