The result sent a seismic shockwave through the tournament when Williams was sent packing in a 6-2, 1-6, 6-4 fourth-round upset.
Top seed Williams, the overwhelming favourite for the title with her chief rivals already out, appeared to have turned the match around when she led 3-0 in the decider but Lisicki, the 2011 semi-finalist, rallied with a gripping fightback
Williams to the list of big names eliminated early at this unpredictable Wimbledon.
Defending men's champion Roger Federer and Rafael Nadal were knocked out in the first three days - along with Maria Sharapova and Victoria Azarenka on the women's side.
The loss ended Williams' career-best 34-match winning streak and her attempt to capture a sixth title at the All England Club.
The loss came in a Wimbledon that opened with Williams in a public spat with Maria Sharapova and that now includes both making early exits.
Before the tournament started Williams addressed issues stemming from a recent Rolling Stone magazine article, the first in which the author stated that critical remarks Williams made were aimed at Sharapova and another in relation to a 16-year-old rape victim in Steubenville, Ohio – and Sharapova’s reaction to those.