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The match, held at the Sheikh Saad Al Abdullah Al Sabah Sports Complex, brought together the defending champions and last season’s runners-up.
Al Khaleej established a strong advantage in the first half, heading into the break with a 17-12 lead.
Sharjah improved after the restart and reduced the deficit in the second half, but the UAE side was unable to complete the comeback as the Saudi club held on to secure a 32-30 victory.
The result handed Sharjah its first defeat of the tournament and gave Al Khaleej an important opening win in the continental competition.
Sharjah will now turn its attention to its second preliminary-round fixture against Burgan Club on Sunday.
The defending champions will be seeking their first victory of the tournament to strengthen their chances of securing a place in the semi-finals.