Born Jessica Lloyd, she is the younger of two daughters of farmer Allan Lloyd (descended from the Lloyd family of Baynham Hall), and his wife Sue who trained as a dancer but then worked as a nurse. Raine was raised on her father's farm in Eardisley, Herefordshire, in the Wye valley close to the border with Wales. Educated in Hay-on-Wye, Powys, as her father starred in amateur dramatics with the Eardisley Little Theatre, Raine wanted to be an actress from the age of 13. In sixth form she studied theatre at A-Level and a BTEC in photography, and then studied drama and cultural studies at the University of the West of England, Bristol. Turned down on graduation to enter every drama school that she applied to, Raine went to Thailand and taught English as a second language.
Returning home after a year, she applied to the Royal Academy of Dramatic Art a second time and was accepted. Moving to London in anticipation of starting her course, she worked part-time as a waitress and for the telecommunications company BT.
After graduating in 2008, Raine began a successful stage career, initially cast as Lesley Sharp's goth daughter in Simon Stephens's Harper Regan. She then played Tamsin Greig's 16 year old daughter in David Hare's Gethsemane. Raine then played at the National Theatre in Mike Bartlett's Earthquakes in London as teenage wild-child Jasmine; and then as a secretary in the revival of Clifford Odets's Rocket to the Moon. She has also appeared in Ghosts and Punk Rock, for which she won the Manchester Evening News Award for Best Supporting Actress. She played a role in the Young Vic's revival of Middleton and Rowley's 17th-century tragedy, The Changeling. In 2012 Raine starred in Beyond Ballets Russes at the London Coliseum.
Raine is currently starring as the lead character Jenny Lee in the BBC One drama series Call the Midwife. After the success of the first series, she shot a Christmas special and a second series. Raine has been asked to commit to a subsequent series but sees her future in film.
She plays the role of a nanny to Arthur Kipps' son in The Woman in Black.
In radio, she has played Felice in the Murray Gold play Kafka the Musical, broadcast in April 2011 on BBC 3. She also played the part of Kasey in Ed Harris' radio play The Wire, the Wall., first broadcast in Feb 2011.
Raine is a guest star in Doctor Who in a story titled Hide in 2013. Later, she will also appear as Doctor Who's original producer, Verity Lambert, in the drama An Adventure in Space and Time, showing the creation of the series as part of its fiftieth anniversary celebrations.
After meeting during the 2010 National Theatre's production of Earthquakes in London, Raine currently lives with her partner of three years, actor Tom Goodman-Hill.