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2018: Surgery and resurgence; two Majors, return to No. 1 & historic Golden Masters

In January, Djokovic defeated Dominic Thiem at the Kooyong Classic exhibition tournament. At the 2018 Australian Open, he reached the fourth round, where he was upset by Chung Hyeon. In late January, he underwent surgery on his elbow. On 3 March, Djokovic returned to the practice courts, and surprisingly played at Indian Wells only a week later, losing in the second round to Taro Daniel. He then lost to Benoît Paire in the second round of the Miami Open.

Reuniting with longtime coach Marián Vajda at the Monte-Carlo Masters, Djokovic collected victories over Dušan Lajović and Borna Ćorić, followed by a loss to Dominic Thiem. In a press conference, he stated, "After two years finally I can play without pain." After another early exit in Barcelona to Martin Kližan, Djokovic's gradual return to form would appear at the Madrid Masters. With a first round win over Kei Nishikori, Djokovic achieved his first victory over a top 20 player in 10 months; however, he lost in the second round to Kyle Edmund. Going into the Rome Masters with a 6–6 season record, he reached the semifinals before losing to long-time rival Rafael Nadal. He then reached the quarterfinals of the French Open before losing to Marco Cecchinato.

Djokovic began the grass court season at Queen's Club, securing his first win over a top 5 player in almost 18 months by defeating Grigor Dimitrov in the second round. He reached the final where, despite holding a championship point, he lost to Marin Čilić. He also played doubles partnering with longtime friend and rival Stan Wawrinka. Djokovic then entered Wimbledon as the 12th seed, where he reached the semifinals to face Rafael Nadal. Djokovic defeated Nadal in a 5-hour and 17-minute, five-set epic spread over two days, becoming the second-longest Wimbledon semifinal in history, second only to the match between Kevin Anderson and John Isner held earlier on the same day. In the final, he claimed his fourth Wimbledon title and 13th major title overall by defeating Kevin Anderson in straight sets. With the win, he rose 11 ranking spots and re-entered the top 10 for the first time since October 2017. At No. 21, he was the lowest-ranked Wimbledon titlist since Goran Ivanišević in 2001.

After a triumphant grass season, Djokovic started his North American hardcourt swing with a third-round showing at the Canadian Open, losing to Stefanos Tsitsipas. Afterwards, he returned to play the Cincinnati Masters for the first time in three years. In an event plagued by suspended play due to rain, Djokovic defeated the defending champion Grigor Dimitrov, Milos Raonic, and Marin Čilić to reach his sixth final at the tournament and fourth final against Roger Federer. Although Federer was riding a streak of 100 consecutive holds of serve at the tournament, dating back to the 2014 final, Djokovic broke his serve three times to win his first Cincinnati Masters title. With this victory, Djokovic became the first (and, as of 2022, only) player in tennis history to complete the Career Golden Masters — winning all nine ATP Masters events at least once in one's career.

Djokovic was the sixth seed at the US Open. He advanced to his eleventh US Open semifinal in as many appearances, where he overcame Kei Nishikori. Djokovic then defeated Juan Martín del Potro to win his third US Open title and 14th major title overall, tying with Pete Sampras 's tally. With the win, Djokovic returned to the top 3 in the world rankings for the first time since the 2017 French Open.

At the Shanghai Masters, Djokovic defeated Kevin Anderson and Alexander Zverev en route to the title, not dropping a set nor having his serve broken throughout. The win marked his fourth Shanghai title, and his ranking rose to No. 2. On 31 October, Rafael Nadal announced his withdrawal from the Paris Masters due to an abdominal injury, and Djokovic reclaimed the world No. 1 ranking. There, Djokovic defeated Roger Federer in a tight three-set semifinal, but was upset by the unseeded Karen Khachanov in the final. At the ATP Finals, Djokovic was guaranteed a fifth year-end No. 1 ranking following the withdrawal of Rafael Nadal from the event. In the round-robin stage, he defeated Alexander Zverev, Marin Čilić, and John Isner without dropping a set. In the semifinals, he defeated Kevin Anderson to reach his seventh final at the tournament but was upset by Zverev. At the 2018 Mubadala Championship, he scored victories over Karen Khachanov & Kevin Anderson to win the title.