Robson had won the first set in her WTA Hobart opener against Belgium's Yani Wickmayer, but was forced to retire after losing the opening two games of the second set, throwing the world number 46's preparations for the Australian Open into turmoil.
Australia's Samantha Stosur emerged victorious only after a struggle against American Madison Brengle in Hobart, winning the rain-interrupted match 6-7(4) 6-1 7-6(6).
Stosur, the 2011 U.S. Open champion, has not advanced beyond the fourth round at home in the past five years, with six first round exits in 14 tournaments in Sydney, Brisbane and the Australian Open.
She also lost all three of her matches in the Hopman Cup in Perth before entering Hobart, which had attracted a strong field before a rash of late withdrawals.
Pennetta had been due to face Williams in the first round.
"Unfortunately I felt some pain in my wrist in Perth and it hasn't had time to recover so sadly I have to withdraw," Pennetta said.
The 33-year-old Williams was beaten in the final of the Auckland Classic by Ana Ivanovic on Saturday and said she could not have withstood another tournament so went directly to Melbourne to prepare for the season-opening grand slam.
Champion Elena Vesnina, who arrived in Hobart last week to prepare for her title defence, is scheduled to play Puerto Rico's Monica Puig later on Monday.
At WTA Sydney, fourth seed Jelena Jankovic crashed out in the opening round, losing 6-4 6-2 to Russia's Ekaterina Makarova.
Two other former grand slam champions, Svetlana Kuznetsova and Francesca Schiavone, also ended their competitive Australian Open preparations early with first round losses at the Sydney International on Monday.
Double grand slam winner Kuznetsova, who had a good second half of 2013 to enter the Sydney tournament inside the top 20 after battling back from knee injuries in 2012, was surprisingly beaten 6-3 3-6 7-5 by American lucky loser Varvara Lepchenko.
Schiavone, the 2010 French Open champion, was bundled out by Lucie Safarova 6-4 6-4. The 33-year-old Italian was also knocked out of the first round of the Brisbane tournament last week by former world number one Jankovic.
WTA Sydney - Women's Singles Round 1
Carla Suarez Navarro (Spain) beat Paula Ormaechea (Argentina) 3-6 7-6(5) 6-2
Ekaterina Makarova (Russia) beat 4-Jelena Jankovic (Serbia) 6-4 6-2
Lauren Davis (U.S.) beat Jarmila Gajdosova (Australia) 6-4 7-6(8)
Varvara Lepchenko (U.S.) beat Svetlana Kuznetsova (Russia) 6-3 3-6 7-5
5-Angelique Kerber (Germany) beat Dominika Cibulkova (Slovakia) 7-6(5) 7-5
Kaia Kanepi (Estonia) beat Victoria Duval (U.S.) 6-1 6-3
Tsvetana Pironkova (Bulgaria) beat Sorana Cirstea (Romania) 6-4 6-1
Bethanie Mattek-Sands (U.S.) beat Eugenie Bouchard (Canada) 6-4 6-3
Lucie Safarova (Czech Republic) beat Francesca Schiavone (Italy) 6-4 6-4
WTA Hobart - Women's Singles Round 1
Kristina Mladenovic (France) beat Silvia Soler Espinosa (Spain) 6-7(7) 6-4 6-4
1-Samantha Stosur (Australia) beat Madison Brengle (U.S.) 6-7(4) 6-1 7-6(5)
Yanina Wickmayer (Belgium) beat Laura Robson (Britain) 4-6 2-0 (Robson retired)
8-Bojana Jovanovski (Serbia) beat Annika Beck (Germany) 7-5 6-3
Alison Riske (U.S.) beat 4-Anastasia Pavlyuchenkova (Russia) 6-3 6-2
Estrella Cabeza Candela (Spain) beat Karin Knapp (Italy) 7-5 6-4
Garbine Muguruza Blanco (Spain) beat An-Sophie Mestach (Belgium) 6-1 6-1
Casey Dellacqua (Australia) beat Alison Van Uytvanck (Belgium) 6-4 6-4
Zhang Shuai (China) beat Zheng Jie (China) 6-3 6-1
- Sports & Recreation
- Samantha Stosur
- Flavia Pennetta
- Jelena Jankovic
- Svetlana Kuznetsova
- Venus Williams
- Francesca Schiavone