Nadal had promised to unveil a remodelled, improved serve at the first Grand Slam of the year and the new action was going smoothly until he served for the match at 5-3 in the third set only for Duckworth to break to love.
"I mean, there is no time for that, I'm sorry to say", the 2008 victor said.
The second-seeded Spaniard had pulled out of the Brisbane warm-up with a thigh strain to raise doubts about his campaign but he allayed those fears on Rod Laver Arena against an error-prone opponent.
After an injury-plagued 2018, the 17-time Grand Slam champion was back to his devastating old self as he raced through in 2hr 15min.
Big-serving Anderson has lost in the first round in the opening Grand Slam of the year six times, including to Britain's Kyle Edmund last year.
"When I get broken was not because of the serve", said the second seed who dished up just a single double fault.
Five-time Grand Slam victor Maria Sharapova warned she can not be written off at this year's Australian Open after serving a 6-0, 6-0 "double bagel" to Britain's Harriet Dart in the first round Monday.
Chuckling even further, Nadal added: "I know, you were closing your eyes to be more focused on what I was saying".
Fifth-seeded Kevin Anderson won his first match at Melbourne Park since 2015 when he beat Adrian Mannarino 6-3, 5-7, 6-2, 6-1.
Sharapova pounced on the Briton's weak second serve to repeatedly break her opponent, bringing up the first set bagel after 31 minutes.
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"It was a good test for my leg, for my shoulder", she said.
Boulter beat Ekaterina Makarova 6-0, 4-6, 7-6 (6), including 10-6 in the tiebreaker.
Defending champions Caroline Wozniacki and Roger Federer were scheduled to play night matches later Monday.
The 26-year-old Australian won last month's Open wildcard playoff to earn his way into the main draw.
Federer's seventh Australian Open title would be the most by any player.
Scottish former world number one Murray tearfully revealed last week that severe pain from a hip injury was proving too much to bear and he planned to retire this year.
Berdych was the 2010 runner-up at Wimbledon and he twice has been a semifinalist at the Australian Open.
Denmark's Wozniacki broke through for her first Slam title in Melbourne past year, beating Simona Halep in the final, and said she was relishing defending a major for the first time.
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