At 22, Handley founded a global online sports-betting business called Feverpitch which fizzled out, he listed on the venture-style New Capital Market of New Zealand Stock Exchange (NZX),[7] He subsequently led a merger of several companies in the New Zealand childcare sector and formed Kidicorp Group Limited, which backed into Feverpitch.

In 2011, he co-founded the mobile advertising network Snakk Media,[citation needed] which listed on the NZ Alternative Exchange (NZAX) in 2013,[22] becoming one of the first public B-Corporations.

[26][27][28] Handley's application for the governmental role of Chief Technology Officer (CTO) of New Zealand became a political controversy when he applied in 2018.

[35] Soon after, the Government announced that it would not be proceeding with the role after concerns were raised by the business community and NZ entrepreneurs over Derek’s selection, suitability, and credibility,[36] and paid Handley compensation of $107,000 (three months' pay plus reimbursement for moving costs).

Handley said he was "deeply disappointed" by the process but the Government's decision to halt it was understandable due to the concerns raised.

[35] Handley is currently General Partner with Aera VC, a fund which invests in deep-tech ventures underpinned by social impact[37] and the UN Sustainable Development Goals.

[39][40] In 2013, he joined the board of Sky Television, a public company on the Australian Stock Exchange,[41] stepping down from the role in January 2021.

During the process of applying for the Chief Technology Officer position, he moved his family back to New Zealand to live in Auckland.

[6] In November 2017, Handley was granted New Zealand citizenship by the Minister for Internal Affairs, Tracey Martin, under the "exceptional circumstances" provision.