The year 2006 was a mixture of some great victories and also a number of defeats. In the Australian Open of the year 2006, Maria lost in the semifinals of the match in opposition with Justine Henin, with the statistics 4-6, 6-1, 6-4; it was the first match she lost after winning the complete first set.

The first title of Maria of the year 2006 was at the Pacific Life Open in Indian Wells, California, it was actually the eleventh one of her whole tennis career. It was then in the finals where Maria won over the other Russian player Elena Dementieva with the triumph statistics 6-1, 6-2. These two finalists then also became the very first Russian players to reach the finals of this event.

It was in the final of Nasdaq-100 Open where Maria lost the match in opposition with Svetlana Kuznetsova, with the statistics of 6-4, 6-3. Unfortunately this match was of great importance for her to win. If she had on the title she would have been the third player to win the Indian Wells-Miami double in the books of history.

Maria then participated in the French Open match of the year 2006, without have a practice of playing any of the clay court tune up matches. She reached the fourth round of the tournament, defeating Mashona Washington, but then was eliminated in the fourth round playing with Dinara Safina, with the statistics 7-5, 2-6, 7-5, after Sharapova led 5-1 in the third set. The time of the year was a bad one for Maria's career where she lost 18 of the 21 points that year.

Maria then was excited for the beginning of the third grass season, but she failed to be victorious for the third successive time in the Birmingham title, losing in the semifinal of the tournament in opposition with American Jamea Jackson.

It was then for the second time consecutively that Maria got defeated in the semifinal of the Wimbledon, losing to the winner of the match Amelie Mauresmo with the statistics 6-3, 3-6, 6-2.

Maria then won the second title of the year 2006 at the Acura Classic in San Diego where she defeated Kim Clijsters with the statistics 7-5, 7-5. It was of great importance to Maria because she had played with Kim for the past five times and this was her very first victory ever since she had met him. It is very well believed that this victory was a turn around for Sharapova's record of that year.

Her only summer hard-court lost in the year 2006 was at Los Angeles where she was defeated by Elena Dementieva in the semifinal round of the event.

Maria then went on to participate in the U.S open tournament of the year 2006, where she seeded third after the champion Kim Clijsters dropped out due to a wrist injury, this was an advantage to her as she was given place in the finals She emerged victorious in the Semifinals of the U.S open after defeating Mauresmo, who was known to be one of the top ranked players of the year with the statistics 6-0, 4-6, 6-0.

She then carried on with the final of the tournament where she defeated Henin with the statistics 6-4, 6-4; this made her win the second Grand Slam title of her career. She was honored to be a part of the list of those players who had beaten the world ranked top players to eventually win the Grand Slam. She was also known as breaking a record of defeating top two world players in a row.