In May 2016, AFC Ajax announced that Bosz was appointed to serve as the new head coach from July 2016 after signing a three-year contract. In his first competitive match as head coach, Bosz's side earned a 1–1 draw against PAOK in the Third qualifying round of the Champions League on 27 July 2016. Bosz was unable to lead Ajax to the group stage of the Champions League after losing 5–2 on aggregate to Russian side FC Rostov. On 11 September 2016, Bosz faced his former side Vitesse, as Ajax won 1–0. On 24 May 2017 Ajax were beaten 2–0 at Friends Arena, Stockholm in the Europa League final by Manchester United.