Kokkinakis ended the year with a ranking of 80. On December 24, 2015, Kokkinakis announced that he would sit out the entire Australian summer of tennis, including the Australian Open, due to an ongoing left shoulder injury. Kokkinakis also missed the 2016 French Open and 2016 Wimbledon Championships. Kokkinakis' first competitive match in 2016 came at the 2016 Summer Olympics, where he lost in the first round to Gastão Elias. On August 25, Kokkinakis announced he would miss the US Open due to a pulled pectoral muscle. Kokkinakis later announced his injuries were caused by vanity, as he lifted weights to increase his bicep size especially with the news that Nike was bringing out new sleeveless tops. Kokkinakis' made his comeback at the Brisbane International after receiving a wildcard in doubles with Jordan Thompson. The duo made it to the final, defeating the top seeds en route, where they won the title, the first Australian duo to win the Brisbane International, defeating Gilles Müller and Sam Querrey. Kokkinakis was granted a singles wildcard at the Apia International, where he was scheduled to play Thompson in the first round, but withdrew due to injury. He subsequently withdrew from the Australian Open. In May, Kokkinakis returned to competitive play in doubles with Alex Bolt at Bordeaux Challenger where they reached the quarterfinals. Using a protective ranking, Kokkinakis played his first singles match since October 2015 at Lyon losing to Denis Istomin in straight sets. In June, Kokkinakis defeated Mikhail Youzhny at ‘s-Hertogenbosch. This was his first ATP tour win since August 2015. In the second round, he lost to Daniil Medvedev. The following week, Kokkinakis received a wildcard into Queen's where he defeated Milos Raonic in his opening match in straight sets to record his first top 10 victory. He lost to Daniil Medvedev in the second round for the second consecutive week. Entering the Los Cabos Open as a wildcard, Kokkinakis first defeated world no. 60 Frances Tiafoe in straight tie breaker sets. He then followed that with two more wins over Peter Polansky and Taylor Fritz to reach the semifinals. He then upset the first seed and Wimbledon 2017 semifinalist Tomas Berdych to reach his first ATP final, losing to Sam Querrey. In August, Kokkinakis lost in round 1 of the US Open to Janko Tipsarevic.