Safina lost to Williams in the final of this year's Australian Open
Russia's Dinara Safina will move to the top of the world rankings after Serena Williams' surprise first-round exit at the WTA event in Marbella.
The 22-year-old, currently ranked second, will overtake Williams when the new Women's Tennis Association list is published on 20 April.
Safina will become the 19th woman to hold the top spot.
Williams conceded her crown with a 6-4 3-6 6-1 defeat against world number 95 Klara Zakopalova on Wednesday.
Safina will be only the second Russian woman after Maria Sharapova to become world number one, and Dinara and Marat Safin are the first brother and sister in tennis history to reach the top ranking.
I hope to prove to everyone over the coming months that I merit the honour of being world number one
But the Russian has yet to win a Grand Slam title, despite reaching the finals of the Australian and French Open over the last year.
"It's a great honour to reach the number one ranking and it is a dream that every girl who has ever wanted to play professional tennis shares," said Safina, who was the runner-up to Williams at the Australian Open this year.
"It is even extra special for me since my brother Marat was able to reach the number one ranking (in 2000) and I am happy to share this achievement with him.
"There's no question that while I am very proud of my results over the past year, I would have liked to reach this achievement in a different manner.
"I hope to prove to everyone over the coming months that I merit the honour of being world number one."
Williams' shock loss to 26-year-old Czech Zakopalova came in her first clay-court match of the season, and followed her defeat by Victoria Azarenka in the Miami final on Sunday.
The American was hampered by a thigh injury that day, and it was a surprise to see her back on court in Spain only three days later.
"The injury prevented me from reaching my top level," said Williams. "I really wanted to play here.
"I know that there's been a lot of advertisement and I wanted to stick to my commitment. I wanted to come to Marbella - I've never been here and I have a lot of fans here.
"It was a great opportunity for people to see me play and I'm really disappointed."
Zakopalova had only won two Tour matches in 2009 before this week. She went into Wednesday's encounter having lost both of her previous meetings with Williams.