Creamer was born in Mountain View, California,[4] and raised in Pleasanton, the only child of an airline pilot father and stay-at-home mother.

[5][7] During Creamer's amateur career, she won 19 national tournaments, including 11 American Junior Golf Association events,[6][8] and was named Player of the Year by the AJGA in 2003.

[9] In December 2004 Creamer won the LPGA Final Qualifying Tournament by five strokes to secure membership on the Tour for the 2005 season.

[16] In August Creamer won the NEC Open on the Japan LPGA tour,[17] and added a victory at the Masters GC Ladies tournament two months later.

[11] Creamer won the LPGA Rookie of the Year award for her season,[13] in which she earned over $1.5 million, second on the money list behind Annika Sörenstam, and recorded eight top-three finishes.

[20] After her strong first-year performance, Creamer was second behind Sörenstam in the inaugural Women's World Golf Rankings, which were released on February 20, 2006.

[22] Creamer still managed to earn over $1 million and make the cut in all 27 LPGA tournaments in which she played, compiling 14 top-10 finishes.

On February 17, she won her third career LPGA title at the SBS Open at Turtle Bay, making a 40-foot birdie putt on the 17th hole of the final round to defeat Julieta Granada by one shot.

In February 2008, she earned her fifth LPGA title at the Fields Open in Hawaii, coming back from a late two-shot deficit with birdies on the final three holes.

[28] On April 27, Creamer came up short in a bid for her second win of the year, losing in a sudden-death playoff to Sörenstam at the Stanford International Pro-Am.

[30] At the U.S. Women's Open, she entered the final round one shot off the lead and in good position to claim her first major championship victory.

[31] On July 10 at the Jamie Farr Owens Corning Classic, she shot an 11-under 60, just one stroke off of the LPGA Tour record of 59 by Annika Sörenstam.

[33] Creamer's fourth title of 2008 came in October's Samsung World Championship, where she won by one stroke and became the first American with four or more wins in an LPGA Tour season since Inkster had five tournament victories in 1999.

[35] At the LPGA Playoffs at the ADT, the last event of the 2008 season, Creamer was hospitalized with a stomach ailment, which was originally thought to be peritonitis.

Her highest finishes during the season were a pair of second-place results, at the LPGA Corning Classic and Lorena Ochoa Invitational.

[39] Creamer withdrew from the first event of the 2010 season with a left thumb injury, which she had first sustained in June 2009 at the Wegmans LPGA tournament.

During the surgery, more severe damage to her thumb was discovered, including ulnar collateral ligament and palmar plate tears.

Her highest finishes of the year were a pair of ties for second, at the RR Donnelley LPGA Founders Cup and CME Group Titleholders.

[51] Creamer's 2014 began with two T-3 finishes in her first two tournaments, the ISPS Handa Women's Australian Open and the Pure Silk-Bahamas LPGA Classic.

[55] After a stretch of four straight missed cuts, Creamer fell outside the top 40 in the world rankings by September 2015; she was dealing with the effects of swing and equipment changes.

[55] Despite not qualifying on points for the 2015 Solheim Cup team, Creamer was chosen for her sixth appearance in the event as a captain's pick.

[56] As part of a U.S. comeback from a 10–6 deficit entering the final session, she contributed the Cup-clinching point with a win in her singles match.

She tied for fourth place at the JTBC Founders Cup, before going into an extended slump in performance in which she missed the cut seven times.

She was forced to play in a qualifier to earn a spot in the Women's British Open, and did not make the initial 2017 Solheim Cup team.

[67] After skipping the entire 2020 season to heal wrist and thumb injuries, Creamer returned to play some events in 2021,[68] making one cut in seven tournaments she competed in.

[9] Creamer ranked outside the top 100 in putts per round in 2012,[49] and Golf World magazine's Ryan Herrington described her putting as "sometimes balky".

[6] While she was the LPGA leader in greens in regulation in 2009 and was regularly high in the tour rankings for the statistic early in her career, by 2014 she fell to 51st.

[80] Her likeness has been featured in EA Sports' Tiger Woods PGA Tour series of golf video games.