Djokovic's embarrassing US Open default remains the only blemish on a record of 29 wins from 30 matches in 2020.
But he did not have things all his own way against an opponent playing his first main draw at a Masters 1000 event, wirth Djokovic having already been taken to three sets by fellow Serbian Filip Krajinovic on Friday.
The world number one targeted Koepfer's backhand as he raced into a 4-0 lead, only for the 26-year-old German to claw back both breaks.
That set the tone for an up-and-down affair, with Djokovic reasserting himself with the forehand to deny Koepfer another game in the first set.
Djokovic had an early advantage in the second but Koepfer levelled up at 3-3, passing his illustrious foe with an eye-catching crosscourt backhand, and the underdog's fourth break of the contest set up a decider.
The relentless pace took a toll on Koepfer as he coughed up a love service game at 1-1 and Djokovic powered home from that point, landing a backhand drop volley to convert his second match point.
Halep was leading the two-time defending champion 6-0 2-1 in Rome when Pliskova retired in tears because of injury.
The Czech called a medical timeout between sets and had treatment on her lower back and leg.
It is Halep's third consecutive title, with the two-time grand slam champion on a 14-match winning streak after a triumph that further solidifies her status as French Open favourite.
The 2018 Roland Garros champion is not willing to burden herself with the weight of expectation despite her hugely impressive form.
"It's just another tournament," Halep said. "I'm not going to put pressure on myself. I've played really well this year, with three titles already.
"I've played so much on clay, so I feel confident and happy that I'll have a chance to play another grand slam this year.
"I'm not going to let myself be bothered by things like the weather. I'll just be happy to take positives from this tournament and go there smiling.
"It's a dream for everyone to win the grand slam tournament from the first day, so it's my dream as well, but I'm not thinking that far.
"I just want to go there, get used to the courts and the atmosphere, and try to win every match I play. Every match is a battle, so I'll be ready for it."
Pliskova had won three of the previous four meetings with Halep but was full of appreciation for the Romanian after falling short this time around.
"Disappointing for me to not finish today, but Simo, obviously too strong," said Pliskova.
"I always have to be 100 per cent to play a good match against you. Congratulations for the whole week. I think you deserve the title."
