He first rose to prominence in the West End, earning a nomination for the Laurence Olivier Award for Best Newcomer in a Play for his performance in the production of Oklahoma!

He received Tony Award nominations for his roles on Broadway playing Yvan in Art (1998), Tevye in Fiddler on the Roof (2004), and Mark Rothko in Red (2009).

His other notable films include Prick Up Your Ears (1987), Enchanted April (1992), Boogie Nights (1997), Chocolat (2000), Luther (2003), The Da Vinci Code (2006), and Love Is Strange (2014).

His parents were both immigrants: his Spanish father —from Murcia— was a waiter who had parachuted into France with SOE before D-Day, and his Italian mother worked as a cleaner.

[2] He decided to become an actor after seeing Spartacus at the age of nine, and attended the Guildhall School of Music and Drama,[9] as well as auditioning for and becoming a member of the National Youth Theatre.

"[15] However, his big break came with Letter to Brezhnev (1985), which he followed with a starring role in Prick Up Your Ears (1987), playing Joe Orton's lover (and eventual murderer) Kenneth Halliwell.

With a midwestern American accent, Molina starred alongside Betty White in the US television series Ladies Man, which ran from 1999 to 2001.

[17] In 1993 he appeared in the BBC miniseries adaptation of A Year in Provence, playing the annoying Tony, along with John Thaw and Lindsay Duncan.

[18] In 1995, Molina starred with Marisa Tomei in The Perez Family, playing Cuban refugees who pretend to be married so they can more easily stay in America.

He played himself alongside Steve Coogan in Jarmusch's Coffee and Cigarettes (2003) and gained further commercial recognition when he portrayed Johann Tetzel in Luther (2003) and Otto Octavius / Doctor Octopus in Spider-Man 2 (2004),[23] which became one of the highest-grossing films of that year.

In 2006, Molina portrayed Touchstone in Kenneth Branagh's film version of Shakespeare's As You Like It and appeared in Ron Howard's adaptation of The Da Vinci Code.

[24] Molina's stage work has included two major Royal National Theatre productions, Tennessee Williams' The Night of the Iguana (as Shannon) and David Mamet's Speed-the-Plow (as Fox).

This serialised novel was written by a team of 15 best-selling thriller writers, including Jeffery Deaver, Lee Child, Joseph Finder and Lisa Scottoline.

[34] In 2017 he portrayed film director Robert Aldrich in Ryan Murphy's FX limited series Feud: Bette & Joan.

In 2020, Molina appeared in David Oyelowo's drama The Water Man, and Emerald Fennell's black comedy thriller Promising Young Woman.

[35] Molina later confirmed that he would actually be reprising his role as the Spider-Man 2 incarnation of Doctor Octopus in No Way Home, retconning his character's apparent death at the end of the former film.

[36] On 2 September 2021, it was announced that Alfred Molina was set to star in Amazon Prime police drama series Three Pines, which comes from The Crown producer Left Bank Pictures.

Molina co-starred alongside Steve Carell, William Jackson Harper, Alison Pill, Anika Noni Rose, and Jayne Houdyshell.