The No 1 seed, who is bidding to win the clay tournament for an 11th time and a third year in succession, has not played on the tour since he retired with a hip injury in his Australian Open quarter-final clash against Marin Cilic.
But after two impressive victories for Nadal in Spain’s Davis Cup quarter-final win last weekend, the 31-year-old secured an emphatic 6-1, 6-3 victory against the former British number two to ease his way into the last 16.
Awaiting Nadal in the next round will be Russian Karen Khachanov after his 6-2, 6-2 win against France’s Gilles Simon.
Earlier, 12-time Grand Slam winner Novak Djokovic booked his place in the third round by seeing off Borna Coric in straight sets.
Djokovic, who ended a three-match losing streak with victory over Dusan Lajovic in his opening rubber earlier this week, secured his progress with a hard-fought 7-6 (7/2), 7-5 victory against the world number 39.
The match lasted more than two hours, and Djokovic, playing in only his fourth tournament since last summer’s Wimbledon championships, required 10 match points to get his victory over the line.
The ninth seed will now face Dominic Thiem for a place in the quarter-finals, with Nadal then to be the likely opponent.
There were also round of 32 victories for Japan’s Kei Nishikori after he clinched a 7-5, 6-2 victory against Daniil Medvedev of Russia.
Roberto Bautista-Agut, the No 11 seed, defeated his Spanish compatriot Feliciano Lopez, but Italian Fabio Fognini, seeded 13th, was on the wrong end of a 6-4, 6-2 defeat to Germany’s Jan-Lennard Struff.
Home favourite Richard Gasquet ran out a comfortable 6-2, 6-1 winner against Argentine Diego Schwartzman, while German Philipp Kohlschreiber, Italian Andreas Seppi, and No 14 seed Milos Raonic also all progressed to the last 16.
Meanwhile, Maria Sharapova has officially joined the field for this summer’s Nature Valley Classic in Birmingham.
Lawn Tennis Association chief executive Michael Downey caused ructions, not least in his own organisation, last year with his decision to offer Sharapova a wild card following her return to the sport after a 15-month doping ban.
Sharapova subsequently had to pull out through injury but signed a two-year agreement and joins a strong field including Wimbledon champion Garbine Muguruza, British No 1 Johanna Konta and Petra Kvitova, who claimed an emotional victory at the Edgbaston Priory Club last June.
Sharapova, who won the Birmingham title in 2004 and 2005 and last played eight years ago, said: “I’m excited to return to play the Nature Valley Classic. I feel like the fans in Birmingham and I go back a long way and I’ve got a lot of good memories of playing there. It’s going to feel really good to be back out there.”
It has been a tough season for the Russian, who has struggled for form and fitness and is ranked 42 nearly a year after beginning her comeback.
Birmingham, which runs from 18-24 June, is set to be her first tournament on grass since she reached the semi-finals of Wimbledon in 2015.