The world number one fell on his left side while hitting a forehand on the baseline and his shot went into the net to allow Sousa to pull even at 4-4.
But Djokovic was not injured and he dusted himself off and won eight out of the next nine games in a 77-minute match. The Serb is vying to match Andre Agassi’s tournament record of six wins in Key Biscayne.
"That first set came down to a few points," said Djokovic after improving to 24-1 in 2016.
"After that, it was quite a good performance. In the second set I felt much more comfortable. I was serving very well the entire day.
"I'm glad that I managed to finish the match the way I did. Obviously, it gives me confidence for the next one."
Djokovic landed 86 percent of first serves in the second set and dropped only three points on serve.
