Twenty-year-old Mladenovic put former champion Sharapova under intense pressure in the opening set before the class of the world No 3 began to tell, resulting in a 7-6 (7/5), 6-3 victory for the Russian.
Fifth seed Sara Errani became the first major casualty as she was upset by teenager Monica Puig.
Italian Errani, who reached the semi-finals of the recent French Open before losing to eventual winner Serena Williams, went down 6-3, 6-2 to her 19-year-old Puerto Rican opponent.
Victoria Azarenka had an injury scare after hurting her knee in a fall on Court One. The second seed, who has been a losing semi-finalist in each of the last two years, was a set and a break ahead of Portugal’s Maria Joao Koehler when she fell awkwardly at the back of the court. It appeared she had suffered a knee injury that might end her involvement in the tournament, but after a long period of treatment the Belarusian ploughed on and clinched a 6-1, 6-2 win.
Serbian 12th seed Ana Ivanovic rode out a testing opening set against France’s Virginie Razzano before tying up a 7-6 (7/1), 6-0 win.
Great Britain’s Anne Keothavong failed in her bid to reach Wimbledon’s second round for a third straight year after falling to Garbine Muguruza on Centre Court. The 29-year-old wild card has progressed from the first round on four previous occasions in her career but was unable to match that achievement this year as the Spanish world number 59 won their first round clash 6-4, 6-0.
Serbian 16th seed Jelena Jankovic ousted another British hope when she defeated Johanna Konta 6-2, 7-5.