The 20-time Grand Slam champion joined Jimmy Connors (1,274), Roger Federer (1,242) and Ivan Lendl (1,068) as the only male players to reach the 1,000-win mark since the Open era began in 1968.
The 34-year-old Nadal achieved another milestone in Paris this year too, having won the French Open last month to tie Federer with 20 major titles.
But while there were 1,000 fans to cheer him on in the final at Roland Garros, none were at the Bercy Arena because of the coronavirus pandemic.
After securing the victory, Nadal touched fists with Lopez and put his rackets into his bag as if finishing a training session, rather than celebrating a huge achievement.
Nadal’s first win came in May 2002 at the age of 15, when he beat Paraguayan Ramon Delgado in the first round at Mallorca.
A year later, the 16-year-old Nadal stunned the tennis world by beating French Open champion Albert Costa under floodlights in the second round at the Monte Carlo Masters.
By the age of 24, he had reached 500 wins, while his career tally also includes 35 Masters titles and 86 tournament victories overall.
The 39-year-old Lopez won their first meeting in 2003 and had beaten Nadal four times overall. He had 22 aces and troubled a sluggish Nadal, who failed to convert six break points in the second set but broke immediately at the start of the third.
Alexander Zverev joined Nadal in the third round by beating Miomir Kecmanovic 6-2, 6-2. The fourth-seeded German did not face a break point against the 42nd-ranked Serb, hit eight aces and converted his first match point. Chasing a third title of the year, Zverev next faces Adrian Mannarino of France.
Fifth-seeded Andrey Rublev easily won 6-1, 6-2 against Radu Albot for a tour-leading 40th win of the year, moving one ahead of top-ranked Novak Djokovic. Rublev won the Erste Bank Open in Vienna on Sunday for a tour-leading fifth title of the season and next plays either three-time Grand Slam champion Stan Wawrinka or unseeded American Tommy Paul.
No. 6 Diego Schwartzman beat Frenchman Richard Gasquet 7-5, 6-3, keeping the Argentine on course to clinch the final spot for the Nov. 15-22 ATP Finals in London. He can guarantee that by reaching the semifinals in Paris.
No. 10 Milos Raonic also advanced by winning 6-4, 6-4 against Frenchman Pierre-Hugues Herbert. The big-serving Canadian, a runner-up here in 2014, had 11 aces and concluded with a sliced volley at the net. He next faces American Marcos Giron.
No. 16 Alex de Minaur also advanced with a 6-3, 7-5 win over Italian Lorenzo Sonego, the runner-up to Rublev on Sunday.