The competition will start on September 13 and is aimed at increasing the participation of girls in the game.
Eighteen clubs will be fielding around 50 teams in age groups from under-8s to under-17s.
The new league sees the merger of the North Staffordshire Girls' League, the Staffordshire County Girls' League and a Walsall-based league.
The new league has met with a mixed reception from established clubs.
Simon De-Winton, who manages Sanford Hill under-12s and is also chairman of the North Staffordshire Girls' League, opposed the changes at the inaugural meeting.
He argued that parents would find it hard to transport their children up to 40 miles in a county-wide competition.
However, Rob Pilkington, chairman of Bradwell Belles Ladies, believes the new league is a huge step forward for girls' football.
He said the league, which has been three years in the making, will keep football accessible to youngsters.
The football for the older age groups – under-14s, 15s, 16s and 17s – will be played on a home and away basis and will be the normal 11-a-side.
Pilkington said: "This has been the norm for a number of seasons and has worked, so the clubs won't have to change too much other than the administration side of things."
The under 8s, 10s, 11s and 12s will play at a central venues.
Pilkington added: "As there are a large amount of teams in the north and south of Staffordshire, each of these age groups will be split so that the teams in both areas will play the teams in their area at a couple of venues.
"The change is they will join up several times in the season and get to play the other teams from the different areas of Staffordshire at a central venue in between the north and south regions – at Rowley Park in Stafford or at St George's Park in Burton."
Pilkington said this would give the girls the opportunity to play against different teams, as well as giving the coaches the chance to meet up with the FA and get the chance to work on their own personal development skills.
The younger age groups will field smaller teams, in accordance with FA guidelines.
The 18 clubs competing in the new league include Leek Town, whose girls enjoyed an immensely successful 2013-14 season.
The club's under-16s team pulled off an incredible treble, winning the Staffordshire League championship and cup, and the Staffordshire Cup.
Since then, the girls have gone on to win the Wyrley five-a-side tournament and bow out at the semi-final stage of a national seven-a-side tournament in Blackpool.
Leek also field younger age group girls' teams and won the North Staffordshire League under-13s/14s tournament, beating Norton United 1-0 in the final.
The other clubs taking part are: Bradwell Belles, Burton Albion, Bilbrook, Chasetown, Congleton Vale, Midlands Soccer Academy, Penkridge Juniors, Shamblers, Stafford Town, Stoke Town, Wyrley Juniors, Burntwood, Phoenix, Lichfield Diamonds, Hednesford Town, Hamil Road, Woodstar Juniors and Norton United.
The league and Staffordshire FA have organised a festival at the National Football Centre at St George's Park, Burton on August 9 to allow clubs to meet ahead of the new season.
Jodie Allard, the Staffordshire FA inclusion officer, said the FA was keen to increase competition for girls', while also keeping travel distance to a minimum for younger players.
She added: "The creation of this league is part of a larger female football development plan which will be implemented by the Staffordshire FA over the coming seasons."
For more information about the new league, send an email email@example.com, or to Jodie.Allard@staffordshirefa.com.