He then played for the Richmond Hill Stars and the Markham Waxers in the Ontario Minor Hockey Association's Eastern AAA League.

[4] On January 8, 2009, Del Zotto traded along with teammates John Tavares and Daryl Borden to the London Knights in exchange for prospects Christian Thomas, Scott Valentine, Michael Zador and six draft picks.

Del Zotto scored his first NHL goal the next day, against Pascal Leclaire of the Ottawa Senators, in the Rangers' home opener at Madison Square Garden.

As a restricted free agent during the 2012–13 NHL lock-out, Del Zotto signed a temporary contract with Rapperswil-Jona Lakers of the Swiss National League A on October 31, 2012.

[9] In nine games for the Lakers, Del Zotto produced two goals and seven points before returning to North America in anticipation for the shortened 2012–13 season.

Upon a resolution to the NHL lock-out, Del Zotto signed a two-year contract extension with the Rangers on the opening day of training camp on January 13, 2013.

The Flyers made him a qualifying offer to retain his NHL rights and, on July 5, 2015, Del Zotto filed for salary arbitration.

[15] On July 1, 2017, as an unrestricted free agent, Del Zotto signed a two-year contract with the Vancouver Canucks worth $6 million.

On January 16, 2019, Del Zotto was traded by the Canucks to the Anaheim Ducks in exchange for Luke Schenn and a seventh-round pick in the 2020 NHL Entry Draft.

[19] He featured in 12 games with the Ducks, collecting 3 assists before he was moved on at the trade deadline by Anaheim to add depth to the St. Louis Blues in exchange for a sixth-round pick in 2020 on February 25, 2019.

[20] Del Zotto was a part of the extended Blues playoff roster, and watched from the press box as they won their first Stanley Cup in franchise history on June 12, 2019.

[24] In the midst of the Blue Jackets training camp, Del Zotto impressed to secure a one-year, two-way contract on January 10, 2021.

On July 12, Del Zotto was placed on waivers again by the Senators for the purposes of buying out the final year of his contract, making him an unrestricted free agent.