Sharapova started the year at the Australian Open, where she defeated fifth seed Svetlana Kuznetsova to reach the second Grand Slam semifinal of her career.

Sharapova held match points in the third set of her semifinal match, before losing to eventual champion Serena Williams.

In February, Sharapova won back-to-back tournaments, the Toray Pan Pacific Open and the Qatar Total Open, allowing her to reach the top 3 in the world rankings for the first time. In the semifinals of the Tier I Pacific Life Open, Sharapova was defeated by Lindsay Davenport, the first time she had failed to win a game in a match.

The following fortnight, she defeated former world no. 1 players Justine Henin and Venus Williams to reach the final at the Tier I NASDAQ-100 Open, where she lost to Kim Clijsters.

Sharapova made the semifinals of a clay-court tournament for the first time at the Italian Open, where she lost to Patty Schnyder. Sharapova would have become world no. 1 for the first time had she won the tournament.

Sharapova then reached the quarterfinals of the French Open for the second consecutive year, before losing to eventual champion Henin.

On grass, Sharapova won her third title of the year when she successfully defended her title at the DFS Classic, defeating Jelena Jankovic in the final. As the defending champion at Wimbledon, Sharapova reached the semifinals without dropping a set and losing a service game just once, extending her winning streak on grass to 24 matches. However, she was then beaten by eventual champion Venus Williams.

A back injury sustained by world no. 1 Davenport at Wimbledon prevented her from playing tournaments during the summer hard-court season, which meant she could not earn new ranking points to replace those that were expiring from the previous year. Sharapova, although also injured for much of this time, had far fewer points to defend, and so she became the first Russian woman to hold the world no. 1 ranking on August 22, 2005.

Her reign lasted only one week, however, as Davenport reclaimed the top ranking after winning the Pilot Pen Tennis tournament.

As the top seed at the US Open, Sharapova lost in the semifinals to Kim Clijsters, meaning she had lost to the eventual champion in every Grand Slam of the season. However, she once again leapfrogged Davenport to take the world no. 1 ranking on September 12, 2005.

She retained it for six weeks, but after playing few tournaments while injured, she again relinquished the ranking to Davenport. To conclude the year, Sharapova failed to defend her title at the year-end Sony Ericsson Championships in Los Angeles, defeating Davenport in one of her round-robin matches, but ultimately losing in the semifinals to eventual champion Amélie Mauresmo.