In 2003 she appeared at The Old Vic in King Lear playing Cordelia. This was followed by Ophelia in Calixto Bieito's Hamlet, and Helen of Troy in Troilus and Cressida for Peter Stein. She had a supporting role in the film Basil and AKA.

She is the daughter of actor Ronald Pickup, with whom she acted for the first time in 2008 in an episode of Midsomer Murders, and will play Molly, the central role in her Mother's first screenplay "G - Litter" in 2015.

Rachel starred at the Criterion Theatre in The 39 Steps and has worked with Sir Peter Hall several times, including his 2009 revival of Bedroom Farce.

In 2011 she moved to the USA to appear in the Shakespeare Theatre Company's production of An Ideal Husband, and subsequently moved from Washington DC to New York. In August 2011 she made her New York Off Broadway debut in the Irish Repertory Theatre's 20th Anniversary production of Dancing at Lughnasa. Other productions at the Irish Repertory Theatre include Airswimming by Charlotte Jones for "Fallen Angel Theatre" and A Mind Bending Evening of Beckett for Robert Flanagan. In 2014 Pickup played Goneril at the new Polonsky Shakespeare Theatre for Theatre For A New Audience, in Brooklyn New York, opposite Michael Pennington's King Lear, and Amanda in Tony Award-winning Director Darko Tresnjak's, Private Lives at Hartford Stage, CT, opposite American actor Ken Barnett. Most recently Pickup played Portia in The Merchant Of Venice at Shakespeare's Globe Theatre in London, England, opposite Jonathan Pryce, directed by "Jonathan Munby". The independent feature film Chronic directed by 2012 Un Certain Regard winner Michel Franco, was part of the official selection for Cannes Palme d'Or 2015. She appeared in a cameo role as Fausta Grables in Wonder Woman.