Lt Col Lucy Giles, 46, will be at the helm at New College to help prepare young British Army officers for their chosen regiments.
She said: "I have to pinch myself really, because it's an enormous privilege to be in this unique position."
The academy was founded in 1947 after two older military institutions merged.
Lt Col Giles from Wincanton, Somerset, will oversee the academic programme and the physical training aspects of the intermediate and senior terms of the course.
The married mother-of-two said: "It's interesting to see people's reactions in this traditionally male environment. I'm a mother and wife of a soldier, so I am bound by juggling those domestic considerations as well as delivering a day job, so to speak."
She said she would "lead by example" and encourage permanent staff to "try and make time for their families".
During her 24-year career Lt Col Giles has led soldiers on operations and deployments in Bosnia, Iraq, Afghanistan, Sierra Leone, East Timor, South Africa and Northern Ireland
She spent two years as the first female Officer Commanding at 47 Air Dispatch Squadron.
She said: "I like to think I was boarded for this appointment because I had the right key skills, knowledge, and experience to be able to do this effectively, as opposed to me being here because I'm female.
"Although, I recognise that being in this position means I may come across as a role model for our future female officers."
Famous royals to have trained at Sandhurst include Princes William and Harry.

The Ibrox outfit cut the gap to nine points with Sunday's win.
"We have six very important league games and it's important we go right through the line this season," Dons manager McInnes told BBC Scotland.
"Hopefully a Hampden cup final and finishing in second spot - I firmly believe that we will do that."
The Pittodrie side, who face Hibernian in the Scottish Cup semi-final on 22 April, went into Sunday's game having won 10 home league matches in a row.
Rangers shaded the first-half chances but the hosts were well on the front foot when Kenny Miller scored the visitors' opener after 79 minutes. The striker added a second two minutes later and substitute Joe Dodoo made it 3-0 in 83 minutes.
McInnes admits he was taken aback by the sudden turnaround and was disappointed by the manner in which his troops responded.
"I think we had real control of the game," he added. "I thought we were better team, certainly in the second half. We started both halves really well but we allowed the first half to get a bit untidy and we didn't pass the ball the way we normally do at home.
"We started the second half strongly and the game was played in their defensive third. Their keeper made a couple of very good saves, particularly from (Adam) Rooney - I thought it was past him to be honest.
"When I was contemplating changes at 0-0 I didn't feel a threat and I thought the goal was coming but unfortunately for us we played a part in our own downfall by giving away a poor goal and we had a crazy five minutes after that.
"Our reaction to losing the first goal was what I'm most disappointed with. From being in charge of the game and looking the most likely we've allowed Kenny Miller the opportunity to show his quality, and he showed it.
"Mentally we've got to be better than that. We normally respond well to going behind - it doesn't happen too often but we have to react better than that and if there's one lesson from today, it is that.
"It's a sore one for us, no doubt about it. In the eyes of our supporters that's a huge disappointment today and we understand that.
"We lost the fight today but it's important we still win the battle for second place, and hopefully get ourselves into a cup final
"We've been on a very good run but that doesn't give you any guarantees, and it's a reminder that there is still work to be done. When you lose a game like today and the huge feeling of disappointment, wishing we could play it all over again, we've got to channel that the right way. We have plenty to look forward to."
The Royal Military Academy Sandhurst has appointed the first female college commander in its history.
[NEXT_CONCEPT]
Derek McInnes is convinced his Aberdeen side will finish second in the Premiership, despite their 3-0 home defeat to third-placed Rangers.