With clay dust swirling around the tree-lined Foro Italico courts, the American former world number one suffered a scrappy, undignified exit as her fabled power game misfired.
Robson will now try to complete a rare double as top seed Serena Williams, winner in Madrid, awaits in round two.
Venus, who has been out of action since early April when she lost to sister Serena in the semi-finals at Charleston, lost her serve three times in the first set and conceded the opener with two wild forehands that landed metres over the baseline.
Robson, who returned to form in Madrid with a notable win over world number three Agnieszka Radwanska after a series of early defeats following a strong run at the Australian Open, was the more solid of the two in the swirling breeze.
The 32-year-old Williams continued to struggle and dropped serve to trail 3-1 in the second set when Robson belted a forehand on to the baseline.
Robson, 19, who recently split from coach Zeljko Krajan after nine months, wobbled when serving for the match at 5-1, throwing in an eighth double-fault.
Two Williams double-faults in the following game allowed Robson to reach match point but she made a hash of the first one before Williams saved a second with a thumping forehand winner.
Robson completed victory at the third attempt with a simple forehand put-away off a loopy Williams miss-hit.
Ninth seed Samantha Stosur eased through with a 6-2 6-3 win over Hsieh Su-Wei of Taiwan while Italian wildcard Nastassja Burnett, ranked 141, enjoyed a surprise 6-2 6-2 win over France's Alize Cornet.
In the men's draw Marin Cilic was one of the few seeds in action on Monday, the Croatian seeing off Kazakhstan's Andrey Golubev 6-4 6-2.
Men's top seed Novak Djokovic will hope to make up for an early defeat in Madrid when he begins in the second round on Tuesday against either Spain's Albert Montanes or Slovakian Martin Klizan.
Rafael Nadal, winner of four claycourt titles already this season after returning from injury, will begin with an Italian opponent in round two, either Fabio Fognini or Andreas Seppi who were battling it out later on Monday.
WTA Rome results
Simona Halep (Romania) beat Svetlana Kuznetsova (Russia) 6-1 6-1
Jelena Jankovic (Serbia) beat Tsvetana Pironkova (Bulgaria) 6-3 6-0
9-Samantha Stosur (Australia) beat Hsieh Su-Wei (Taiwan) 6-2 6-3
Melanie Oudin (U.S.) beat Ekaterina Makarova (Russia) 2-6 7-5 4-2 (Makarova retired)
Garbine Muguruza Blanco (Spain) beat Mathilde Johansson (France) 1-6 6-0 6-2
Nastassja Burnett (Italy) beat Alize Cornet (France) 6-2 6-2
Peng Shuai (China) beat Monica Niculescu (Romania) 4-6 6-3 6-2
Sabine Lisicki (Germany) beat Mallory Burdette (U.S.) 6-1 6-2
Ayumi Morita (Japan) beat Sorana Cirstea (Romania) 6-1 6-3
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