Having already captured the Australian and French Open titles this year, world number one Djokovic is halfway to becoming just the third man in history to complete a calendar Grand Slam.
It’s a feat so rare that Rod Laver was the last man to achieve the sweep back in 1969.
In what could be a record-breaking year for Djokovic, there is also the chance of an Olympic title which could pave the way for a Golden Slam of all four majors and Tokyo gold.
“Wimbledon, Olympics, and US Open can be fun to watch Novak play because he’s going to put everything on himself to try to make it," said world number two Daniil Medvedev.
“That’s when he’s strongest but at the same time that’s a lot of pressure."
First up for Djokovic on Centre Court is Britain’s world number 250 Jack Draper who grew up just six miles (9.5km) down the road from the All England Club.
It will be the 34-year-old Djokovic’s first match on the court since his epic five-set win over Roger Federer in the 2019 final, the longest title match in tournament history and where he saved two championship points.
Elsewhere on Monday, Greece’s Stefanos Tsitsipas, promoted to third seed in the absence of Rafael Nadal, has a tough opener against 56th-ranked Frances Tiafoe of the United States.
Tiafoe won a second-tier grass court Challenger event in Nottingham this month before making the quarter-finals at Queen’s Club.
Tsitsipas, who lost a five-set final to Djokovic at the French Open two weeks ago, made the last 16 at Wimbledon in 2018.
However, he was a first round loser two years ago and comes into Wimbledon with just 15 matches on grass in his career.
Two-time champion Andy Murray is on Centre Court against Georgia’s Nikoloz Basilashvili, a semi-finalist in Halle.
Murray, now ranked at 119, is playing his first singles match at Wimbledon since 2017 after a lengthy battle with hip and groin injuries.
Venus Williams, a five-time champion at the All England Club who played the tournament for the first time in 1997, begins against Mihaela Buzarnescu of Romania.
Williams, 41 and down at 111 in the world, hasn’t won a match on tour since the Australian Open in February.
Petra Kvitova, the 2011 and 2014 champion, starts against former US Open winner Sloane Stephens.
Second seed Aryna Sabalenka faces unorthodox Monica Niculescu of Romania, a top 20 player in 2012 but who now stands at 193.
Although Wimbledon is back on the schedule this year, it will look very different with only 50% capacity until the finals’ weekend when there will be a 15,000 capacity crowd.
Players are also confined to a hotel ‘bubble’ in central London.