Keightley, the England Women's head coach, included allrounder Lamb in a 13-strong squad announced for the Test, starting next Monday in Taunton.
"Emma's really exciting, she's a young player who has been in and around the system," Keightley said. "I just think it's her time and her chance to show us what she's got.
"She also offers spin and she's great in the field so she gives us three facets, which is always good in a Test match. It's pretty obvious that she's going to potentially debut, we'll prep her as best we can. She's got really good performances in regional cricket and now it's just moving up into the internationals and stamp her case on moving forward on why she should be an opener."
Lamb made her international debut during the 2021 English summer, playing her only T20I against New Zealand in September before making two ODI appearances, during this year's Ashes and World Cup.
With Lauren Winfield-Hill overlooked for the Test squad after suffering a dip in form and instead named in a 16-player England Women's A squad for a three-day fixture against South Africa at Arundel from Tuesday, Lamb looks most likely to partner Tammy Beaumont at the top of the order, having filled that role once during the Ashes.
Danni Wyatt, who has also opened with Beaumont in white-ball formats, has never played a Test and was also named in the A squad, which will be captained by Georgia Elwiss with John Stanworth as head coach.
Lamb has enjoyed a strong season for Thunder in this year's Charlotte Edwards Cup T20 competition with two fifties and a score of 42 from six innings. She also took four wickets with her offbreaks at 19.75, with an economy rate of 5.26.
Davies has played seven ODIs and 17 T20Is and was part of England's Ashes and World Cup campaigns earlier this year, while the uncapped Arlott and Bell have been on the fringes of selection for the past year.
"It's over 10 years of those two having the ball and doing what they do," Keightley said of Shrubsole and Brunt. "Throughout that journey, they've both had their ups and downs in form. Generally they're very consistent and you know what you're going to get.
"We don't know what we're going to get but that brings excitement, new opportunities. It's an end of an era and we need to create a new one and see which players are going to stick their hand up and lead the way with the ball. Our hand's been forced and we'll wait and see how it goes."
Davidson-Richards returns to the England set-up for the first time since 2018, when she played one ODI and five T20Is. She was part of the England A side which featured in a series against Australia A concurrent with the Ashes, scoring 72 in a 50-over game, and she also offers a seam-bowling option.
"I think it shows the strength and the importance of regional cricket in the domestic structure and her being able to train full-time," Keightley said. "Batting-wise she's improved her skill, last year in 50-over cricket she just missed out on a hundred and got 99. With the ball, she's got better-skilled, and I think she's found what sort of bowler she wants to be.
"She gives an option of a batting allrounder, and we haven't got too many of those from a seam perspective. We've got a number of options from a spin perspective, but as a seamer Alice has put her hand up for us to have a look at, and as a person I think she's grown over the last four years. She's loving cricket, she's loving being a professional cricketer, and you can see that in her performances."
Issy Wong, the 20-year-old fast bowler with genuine express pace, has travelled with England squads for the past two years as part of her ongoing development. Keightley said Wong was under serious consideration to make her long-awaited international debut this summer, albeit in the white-ball formats and with a view to carefully managing her workload.
"Issy Wong is extremely exciting; she's quick and is the quickest in England," Keightley said. "Managing her through the summer and getting the best out of Issy is probably not playing this format [Tests]. She's in and around because of how exciting she is and the pace that she offers.
"Hopefully for Issy, if she continues to bowl well and make net sessions extremely hard for batters, she's got a good chance of playing in the summer."
South Africa will be playing their first Test in seven years while the upcoming match will be England's third in just over a year, having drawn with both India last June and Australia in January. The Test kicks off their multi-format series, which also includes three ODIs and three T20Is in July with four points up for grabs for winning the Test and two points for each of the limited-overs games.
Valkerie Baynes is a general editor at ESPNcricinfo