Nadal has looked in imperious form throughout the tournament, dropping just 1 set en route to the fourth round.
The Spaniard dispatched of Yuichi Sugita in his opener before battling past a spirited Nick Kyrgios in the second round.
It was much smoother sailing for the French Open champion in the third round though, as he cruised past an insipid Jo-Wilfried Tsonga to book a date with Sousa.
The Portuguese has come through some titanic battles thus far. He saw off British hopeful Paul Jubb in the first round before producing arguably the upset of the tournament by annihilating Marin Cilic in straight sets in the second round.
A marathon five-set victory over Dan Evans holds him in good stead heading into this encounter with the third seed.
Nadal and Sousa have crossed paths two times in the past, with the Spaniard winning both encounters. He dropped only one set in those two matches and enters this contest as the firm favourite.
Here is all you need to know about 2019 Wimbledon:
Tournament name: 2019 Wimbledon Championships
Date: July 1-July 14, 2019
Category: Grand Slam
Location: All England Lawn Tennis and Croquet Club, SW19, Wimbledon, London
Time:  Rafael Nadal v Joao Sousa on Centre Court at 5:30 p.m IST
Where to watch Wimbledon 2019?
USA - ESPN and ESPN2
UK and Europe - BBC1, BBC2, and the BBC Red Button.
Australia - Channel 7
India - Star Sports Select 1/Select 1 HD and Select 2/Select 2 HD.
Live Stream details for Wimbledon 2019
Wimbledon 2019 live stream is available on ESPN for users in USA and Kayo Sports for users in Australia (a subscription is needed for the services).
It will also be streamed live on hotstar.com (India)
The Wimbledon YouTube channel will showcase the behind-the-scenes moments of the tournament and highlights.
2019 Wimbledon Scores, Latest news, and Updates: SportskeedaPublished 08 Jul 2019, 16:45 IST