Top seed and world number one Murray opens proceedings on Centre Court insisting a hip problem will not prevent him from dispatching Kazakh lucky loser Alexander Bublik.
The weekend news that the 30-year-old Scot is to become a father for the second time will also be an extra incentive to make it a tournament to remember.
Nadal, the champion in 2008 and 2010 and a three-time runner-up, missed last year's championships because of a wrist injury.
Since making the final in 2011, he has lost to opponents outside the top 100 on four occasions.
Australia's John Millman, his first round rival on Monday, is the current 137.
Elsewhere on the opening day, former world number one Victoria Azarenka plays her first Slam since becoming a mother while two-time champion Petra Kvitova is sure to receive a warm Centre Court welcome as she steadily rebuilds her career after being attacked by a knifeman in her home last December.
Murray is looking to become the first British player –- man or woman –- to defend a Grand Slam title since Fred Perry won Wimbledon from 1934-36.
Meanwhile, Bublik, the world number 134, is making his grass court debut.
Murray, who has a 29-0 record against players outside the top 100, insists his recent hip problems are behind him.
"I'll be fine to play the event and play seven matches," he said.
Nadal is bidding to record his 850th tour-level match-win and become just the seventh player in history to reach the landmark.
It's also his 50th match at Wimbledon.
Millman is playing just his second match of the year after missing five months with a hip injury.
- Nadal on high after French Open -
Nadal, on a high after his record-setting 10th French Open title just three weeks ago, will not be under-estimating the Australian after his recent experiences at Wimbledon.
The 31-year-old Spaniard lost to world number 100 Lukas Rosol in 2012, number 135 Steve Darcis in 2013, Nick Kyrgios, the 144, in 2014 the 102-ranked Dustin Brown in 2015.
"This is a tournament that you can go out very early. But at the same time, if I am able to go through at the beginning, I think I'm with confidence," said Nadal.
Venus Williams marks her 20th Wimbledon anniversary with a tie against Belgium's Elise Mertens who she defeated in the third round of Roland Garros.
However, the 37-year-old five-time champion arrives in London facing a wrongful death suit after she was involved in a fatal car crash in Florida.
An elderly man in the other vehicle suffered head injuries in the collision and died on June 22.
Kvitova, whose career was almost ended by the injuries caused fighting off an intruder at her home in the Czech Republic, takes on Sweden's Johann Larsson.
In the absence of Serena Williams (pregnant) and Maria Sharapova (injured), Kvitova finds herself in the position of favourite for a third title to add to her 2011 and 2014 triumphs.
Azarenka, who starts against Catherine Bellis of the United States, will be playing her first Grand Slam since taking time off after last year's French Open to have her first child Leo in December.
Kim Clijsters, Margaret Court and Evonne Goolagong are the only women to have won a Grand Slam after having a child.
Elsewhere on day one, men's fifth seed Stan Wawrinka, looking to complete the career Slam faces Russia's Daniil Medvedev while combustible Australian Nick Kyrgios kicks off play on Court Three against Pierre-Hugues Herbert of France.
French Open winner Jelena Ostapenko, the 2014 Wimbledon junior champion, takes on Aliaksandra Sasnovich of Belarus.
Second seed Simona Halep, blasted off court in the Paris final by Ostapenko, faces New Zealand's Marina Erakovic.
source: news.abs-cbn.com
