With Andy Murray sidelined, Edmund has become the British number one and he shone again on clay with a huge win over former champion Djokovic.
Edmund for his part was at his imposing best in a 6-4, 6-0 win over the young Russian Daniil Medvedev in their first round match yesterday.
Djokovic broke serve late in each set to get past Nishikori after almost two hours at La Caja Magica.
He added: "I believe a lot in dynamics, in momentum". It's just a really good win for me. "It was exactly what I needed for my confidence and for my game".
"That's all I can do - go out there and do my best".
Djokovic has struggled this year after saying he returned to action too quickly following a lingering right elbow injury.
In his previous event, he lost in the third round in Monte Carlo, where Nishikori reached the final.
"I don't think [about] victories in a row", insisted the 16-time grand slam champion and French Open favourite. "I just knew that if I put myself in the match hopefully in the closing stages I would give myself a chance. It's great. I couldn't ask for a better start". "That makes me feel strong".
World number one Rafael Nadal has said he is confident of Novak Djokovic halting his inconsistent run and making a step-by-step progress towards returning to peak form in the coming days.
The 31-year-old Russian, who entered the tournament on the back of four consecutive defeats, rallied from 3-1 down before snatching the opening set with a ferocious forehand. The 12th-ranked Serb also failed to advance past the last 16 at the Australian Open. She has been dealing with a left forearm injury.
Jelena Djokovic appeared on Serbian TV on Wednesday morning and said that she is not at fault for her husband's poor form.
"Well, you know, look, there are obvious things that are not working well for me. That will certainly help me moving forward".
Nadal will next face the man he beat in last year's final, Dominic Thiem, after the fifth seed came from a set and a break down to edge out Croatian Borna Coric 2-6, 7-6 (5), 6-4. Wozniacki reached the 2009 final on debut and hasn't been close since.
I mean, in terms of I guess a name, one of the biggest names I've beaten, for sure.
Milos Raonic defeated Nicolas Kicker 6-3, 6-2 to set up a second-round encounter with third-seeded Grigor Dimitrov, while Richard Gasquet beat Tomas Berdych 6-4, 6-2 to advance to play qualifier Dusan Lajovic, who got past Karen Khachanov 6-3, 6-2.