Nadal, playing his first match since limping out of the Australian Open in January with a hip injury, beat Philipp Kohlschreiber 6-2, 6-2, 6-3 in just over two and half hours in Valencia, stretching his winning streak in the Davis Cup to a record 23 matches in singles and doubles.
The victory for the world number one in the Plaza de Toros bullring levelled the tie after world number four Alexander Zverev beat 33rd-ranked David Ferrer 6-4, 6-2, 6-2.
"Of course, it's a positive thing to win in straight sets," said 31-year-old Nadal, who has not lost a singles match in the Davis Cup since his 2004 debut and in doubles since 2005. "I played a solid match. I feel good when I return to the clay courts."
Nadal, building up to an assault on what he hopes will be an 11th French Open title, said it had been a special day playing on home ground again.
"It's a memorable day, in front of my own crowd. It's always special to play in these arenas," added Nadal, who has played in four of Spain's five Davis Cup-winning teams. "It's great to be back even if after an injury it's always difficult."
On Saturday, Marc Lopez and Feliciano Lopez will face Tim Puetz and Jan-Lennard Struff in the doubles, paving the way for a potential tie-deciding clash between Nadal and 20-year-old Zverev on Sunday.
Spain have history on their side -- they have won 26 straight home ties, with their last defeat on Spanish soil against Brazil in 1999.
The winner of the Valencia quarter-final will face either defending champions France or Italy for a place in the final.
35th win for Cilic
Lucas Pouille, the world number 11, gave France the first point in Genoa with a 6-3, 6-2, 4-6, 3-6, 6-1 win over 62nd-ranked Andreas Seppi.
Italian number one Fabio Fognini then won a bad-tempered 3hr 30min rubber against world number 80 Jeremy Chardy 6-7 (6/8), 6-2, 6-2, 6-3 to make the tie 1-1.
Fognini, who spent over 11 hours on court in the victory over Japan in the first round, was furious after Chardy had brushed his shoulder against him during a changeover early in the third set.
"I didn't even know if I really touched him on the shoulder. He made this a huge thing, like in football sometimes where the guy you don't touch still collapses," said Chardy.
Chardy, a surprise selection ahead of Adrian Mannarino, the world 25, suffered his first Davis Cup defeat in six matches.
On Saturday, France's Nicolas Mahut and Pierre-Hugues Herbert will face Fognini and Simone Bolelli in the doubles.
"I am ready to play three days, for sure," said Fognini who has played for Italy every year since 2008. "The Davis Cup is special. I am playing not just for me but also for Italy."
Croatia, the 2005 champions, got off to a winning start against Kazakhstan in Varazdin when world number three Marin Cilic outclassed Dmitry Popko, the world 258, in straight sets, 6-2, 6-1, 6-2.
The victory was Cilic's 35th in Davis Cup, just one short of Ivan Ljubicic's Croatian record of 36.
But Mikhail Kukushkin, the top-ranked Kazakh player at 92, then levelled the tie by seeing off world 28 Borna Coric, 3-6, 7-6 (7/5), 6-4, 6-2.
In Nashville, John Isner and Sam Querrey lifted the Americans a 2-0 lead over last year's runners-up Belgium as the US tries to reach the semis for the first time in six years.
Isner needed three hours and 14 minutes to dispose of world number 319 Joris de Loore 6-3, 6-7 (4/7), 7-6 (10/8), 6-4, while world number 14 Querrey beat 110th ranked Ruben Bemelmans 6-1, 7-6 (7/5), 7-5 in a two-hour long second rubber.
Belgium, who are playing without world No. 10 David Goffin, don't have a player ranked in the top 100 in their lineup.
By AFP's Dave James