Britain's Watson, 48 places below Lisicki in the world rankings, showed little regard for the gulf in status between the two as she blitzed the German's serve and clinched progress to the second round in straight sets 6-4 7-6(3).
After the pair spent most of a closely-fought opening set failing to break each others' serve, it was underdog Watson who finally took advantage of an opening at the third attempt in game 10.
The break handed Watson the set, though Lisicki responded almost instantly with an early break in set two.
The contest opened up from there with four straight breaks of serve in total before Lisicki held serve to stay alive at 6-5 down and force a tie-breaker.
But the 20-year-old surged into a 6-1 lead in the tie-break before clinching her third match point to claim a big scalp in progressing.
It does not get any easier for Watson in round two, however - a contest with second seed and former world number one Maria Sharapova awaits.