The world number one, who claimed victory in the record-breaking 21st Grand Slam Championship, won 6-3 6-1 6-0 in the first night session at the Philip Shatrie Court the day after he turned 35.
Djokovic was unable to play in the Australian Open after being deported from Melbourne, but on Monday in his first major match of the year under fire at Roland Garros came to the ground.
The first seed came in 35 winners as Japanese outsider Nishioka learned his lesson and met Alex Molkan or Federico Coria in the second round.
Djokovic got his first break when his left-handed opponent made a double fault and walked away 4-2, and the Serb conveniently gave the set.
Nishioki had no answer to the two-time French Open champion, and the crowd did the outsider no favors, whistling one of the greatest of all time, seemingly because he was so superior to his opponent.
The passionate Djokovic led 5-0 in the second set, and although Nishioka managed to avoid the bagel, he was unable to play the reigning champion in another completely one-sided third set.
It was a bright victory for Djokovic because of his record crown of the 38th ATP Masters 1000 in Rome.