The 14-time Grand Slam champion sealed a 6-0 4-6 6-3 victory over Sousa, who is ranked 35th in the world.
Nadal breezed through the first set in 26 minutes as he won six straight games, claiming the lead on his third set point.
The second set was not as simple, with games going by the way of serve until Sousa broke to go 5-4 up and eventually drew level on sets.
In the decider, Nadal squandered the chance to take an early break in the second game, but he eventually got the job done to continue his impressive form on clay.
Last month, the 29-year-old won the Monte Carlo Masters and Barcelona Open.