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On 26 August, Henderson became the first Canadian in 45 years – after Jocelyne Bourassa in 1973 – to win the Canadian Women's Open at the Wascana Country Club in Regina, Saskatchewan.
Since 2012, Henderson has been in training with Golf Canada's amateur and young professional development programs called "Team Canada".
After Monday-qualifying for the Cambia Portland Classic in Oregon in August, Henderson won the event by eight shots, the largest victory margin on tour since 2012, and became the tour's third-youngest winner. Henderson was only the second Monday qualifier to win on tour, and the first since Laurel Kean in 2000. She was also the first Canadian to win on the LPGA Tour since Lorie Kane in 2001, and was granted immediate LPGA Tour membership.
She won the Canadian Women's Amateur in 2013, and finished runner-up at the 2014 U.S. Women's Amateur. While still an amateur, she won three events on the CN Canadian Women's Tour and finished tied for 10th place in the U.S. Women's Open at age 16. She won numerous amateur tournaments and was the top-ranked female amateur golfer in the world before turning professional in December 2014, passing up the chance to play college scholarship golf.
Born and raised in Smiths Falls, Ontario, Henderson learned golf from an early age at the Smiths Falls Golf and Country Club. Her parents are both experienced players, while her uncle Tom Henderson competed frequently for many years at the top amateur level in the Ottawa area. Brooke's sister Brittany Henderson, older by seven years, was also a top junior and college golfer. Brooke graduated from Smiths Falls District Collegiate Institute in June 2014.
At age 17, Henderson had to play her way into LPGA Tour events through Monday qualifiers, and to rely on sponsor exemptions, after her request for an age waiver to compete at the LPGA Tour Q School in late 2014 was denied. She earned a Symetra Tour card after winning her first event as a professional, the Four Winds Invitational in Indiana in June 2015. With a final round 66 (−4), Henderson tied for fifth at the U.S. Women's Open in July.
During 2015 to 2016, Henderson was signed to several corporate sponsorships:
Henderson set a tournament record with her 36-hole score at the LPGA Tour's Swinging Skirts LPGA Classic in April 2015, at the Lake Merced Golf Club, just south of San Francisco. Her second round 65 (−7) gave her 135 (−9), breaking the record set by Stacy Lewis in 2014 by three shots. Henderson finished third, one stroke behind Lydia Ko, the playoff winner, and runner-up Morgan Pressel.
In June 2016, Henderson won her first major championship, at the KPMG Women's PGA Championship at Sahalee Country Club near Seattle. Her final round 65 (−6) propelled her into a tie with top-ranked Lydia Ko, followed by a playoff which Henderson won with a birdie on the first hole. She became the youngest to win that major, the second-youngest in any women's major, and the first Canadian to win a major in 48 years. It was Henderson's second tour win, both in the Pacific Northwest, and her first as a tour member; it moved her from fourth to second in the world rankings.
With her win as defending champion at the Cambia Portland Classic in June 2016, Henderson joined Sandra Post and Lorie Kane as the only Canadians to win multiple LPGA events in the same season.
In February 2017, Henderson signed other sponsorship deals with Canadian Pacific, MasterCard, Rolex, BMW, BioSteel, and Golf Town. As of 2017, Henderson became a resident touring professional at Miromar Lakes Beach and Golf Club, Miromar Lakes, Florida.
In June 2017, Henderson won the Meijer LPGA Classic. Henderson's win on 2 October 2017 at the McKayson New Zealand Women's Open was her first LPGA championship outside North America.
By finishing second (to Ariya Jutanugarn) in the 2018 season-ending Race to the CME Globe, Henderson was awarded $150,000 from the bonus pool purse. In December she was awarded the (Bobbie Rosenfeld Award as The Canadian Press Female Athlete of the Year for the third time.
On 20 April 2019, Henderson defended her title at the Lotte Championship in Hawaii. This marked her eighth victory on the LPGA Tour, tying Sandra Post, Mike Weir and George Knudson for the most victories by a Canadian golfer on the LPGA or PGA Tours.
On 16 June 2019, Henderson won the Meijer LPGA Classic in Michigan for the second time – the third LPGA event where she has multiple victories. This was her ninth victory on the LPGA, giving her the most victories on major tours of any professional golfer in Canadian history.
Results not in chronological order before 2019 or in 2020.