The Leeds-based club announced Keightley's appointment shortly after confirming Dani Hazell would leave Superchargers at the end of her contract.
The announcement was made by Keightley's new club on Instagram alongside the caption "Welcome to Leeds, Lisa!"
She became the first female to lead England Women full-time when she assumed the role in 2020, but left at the end of the 2022 summer.
The 53-year-old led England to the final of the World Cup in April 2022, but they could not emulate their 2017 triumph, losing to Australia in Christchurch.
England were also knocked out in the semi-finals of the 2020 T20 World Cup and failed to secure a medal at the Birmingham Commonwealth Games.
Keightley has most recently served as head coach of the Sydney Thunder after signing a three-year contract to lead the Women's Big Bash League side last summer.
She also coached the Scorchers in the WBBL.
As an Australia international, primarily a right-handed batter, Keightley made nine Test appearances and played in 82 ODIs and one T20.
Former England captain Hazell will be the new head coach of Durham Women.
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