- Tag results for Novak Djokovic
Djokovic sent out a warning to his rivals at the ATP Finals on Monday, brushing aside big-serving John Isner 6-4, 6-3.
The two men, with 34 Grand Slams between them, are the twin titans at the season-ending event at London's O2 arena.
Djokovic had secured World No. 1, following Nadal's retirement from the Paris Masters due to abdominal problems.
Khachanov refused to give his opponent the slightest opening, and sealed a memorable victory after an hour and 37 minutes.
Djokovic, who will replace an injury-plagued Nadal at the top of the rankings on Monday, now leads Federer 25-22 overall and has not lost to the Swiss since 2015.
Federer, chasing a 100th career title, moved a step closer to that goal with a 6-4, 6-4 win over Japan's Kei Nishikori in Friday's quarter-finals in the French capital.
Djokovic was guaranteed a return to the ranking summit when Nadal withdrew from Paris with an abdominal injury on Wednesday.
Djokovic takes over as world number one in the latest ATP rankings published Monday from Rafael Nadal, who withdrew injured from Paris on Wednesday.
The Wimbledon and US Open champion becomes the first player to start the season outside the top 20 and end up top of the ATP rankings since Marat Safin in 2000.
Serving for the match at 5-1, Djokovic handed a towel to a man in the crowd who seemed unwell and who wiped his forehead with it.
Djokovic had never dropped a set in five previous meetings with Portugal's Sousa, but he surrendered a 4-1 lead in the opener and appeared under the weather before regrouping to break Sousa at 6-5.
If the holder of 20 Grand Slam titles lines up at Bercy it will be his first appearance at the last Masters' event of the season since 2015.
Roger Federer could also resurface in the French capital after a three-year absence, although the 20-time Grand Slam champion said a decision on his participation will be made on Tuesday.
Djokovic overtook Switzerland's Roger Federer in the standings, pushing him down to third.
Serbia's Djokovic, 31, is in imperious form, winning 16 ATP matches in a row coming into the clash with Zverev, a rising star of tennis.