Having convincingly won the first set, Sonego got the better of the 2018 quarter-finalist after a remarkable tie-break.
Sousa looked to have the edge when he made it 11-10, but Sonego fought back, claiming successive points before breaking serve to wrap up a 6-4 7-6 (13-11) victory.
Miomir Kecmanovic also won his first-round tie, coming through 6-4 6-3 against Jaume Munar.
Viktor Troicki will meet Jozef Kovalik in the first round after the top-ranked qualifier survived a scare from Roberto Ortega-Olmedo.
Troicki fell behind in the first set on Sunday and needed a tie-break to keep himself in the match in the second.
But the two-time Sydney International champion rallied in the third, securing a 3-6 7-6 (7-4) 6-2 win.
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