Mirren, who is nominated for her performance as Queen Elizabeth II in Peter Morgan's The Audience, won an Olivier Award for the role back in April.
Ejiofor's nomination, for A Season in the Congo at the Young Vic, comes as he is being hotly tipped to be in the running for an Oscar next year for his performance in the forthcoming film 12 Years a Slave.
The Best Director category features past, present and future artistic directors of the National Theatre in Richard Eyre, Nicholas Hytner and Rufus Norris; while Lucy Kirkwood's Chimerica, Nick Dear's The Dark Earth and the Light Sky and Lucy Prebble's The Effect are up for Best Play.
The Effect, which premiered it the NT Cottesloe 12 months ago, is also represented by Best Actress nominee Billie Piper and Lyndsey Turner, who is shortlisted for Best Director.
And the newly created Best Musical Performance category is an all-female affair, comprising Rosalie Craig (The Light Princess), Cynthia Erivo (The Color Purple) and Charlotte Wakefield (The Sound of Music).
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The judging panel comprises critics Henry Hitchings, Georgina Brown, Susannah Clapp, Charles Spencer and Matt Wolf, and Evening Standard editor Sarah Sands.
Sands called the shortlist for the 59th awards "one of our strongest in years", adding: "The Evening Standard is proud to play a part in London's theatrical life with these Awards at a time when it is buzzing with so much creativity."
The awards will be announced during a ceremony compered by Homeland star Damian Lewis at the Savoy Hotel on 17 November.
Full Evening Standard shortlists:
Chiwetel Ejiofor for A Season in the Congo (Young Vic)
Rory Kinnear for Othello (NT Olivier)
Adrian Lester for Othello (NT Olivier)
Natasha Richardson Award for Best Actress
Linda Bassett for Roots (Donmar Warehouse)
Lesley Manville for Ghosts (Almeida)
Helen Mirren for The Audience (Gielgud)
Billie Piper for The Effect (NT Cottesloe)
Kristin Scott Thomas for Old Times (Harold Pinter)
Chimerica by Lucy Kirkwood (Almeida & Harold Pinter)
The Dark Earth and the Light Sky by Nick Dear (Almeida)
The Effect by Lucy Prebble (NT Cottesloe)
Ned Sherrin Award for Best Musical
The Book of Mormon (Prince of Wales)
The Light Princess (NT Lyttelton)
Merrily We Roll Along (Menier Chocolate Factory & Harold Pinter)
Richard Eyre for Ghosts (Almeida)
Nicholas Hytner for Othello (NT Olivier)
Rufus Norris for The Amen Corner (NT Olivier)
Lyndsey Turner for Chimerica (Almeida & Harold Pinter)
Bob Crowley for People (NT Lyttelton) & The Audience (Gielgud) & Once (Phoenix)
Es Devlin for Chimerica (Almeida)
Tim Hatley (design) & Peter Mumford (lighting) for Ghosts (Almeida)
Charles Wintour Award for Most Promising Playwright
Rachel De-lahay for Routes (Royal Court)
Rory Kinnear for The Herd (Bush)
Phoebe Waller-Bridge for Fleabag (Soho)
Milton Shulman Award for Outstanding Newcomer
Caoilfhionn Dunne for The Night Alive (Donmar Warehouse)
Seth Numrich for Sweet Bird of Youth (Old Vic)
Luke Thompson for A Midsummer Night's Dream (Shakespeare's Globe)
Olivia Vinall for Othello (NT Olivier)
Best Musical Performance
Rosalie Craig for The Light Princess (NT Lyttelton)
Cynthia Erivo for The Color Purple (Menier Chocolate Factory)
Charlotte Wakefield for The Sound of Music (Regent's Park Open Air)