- Jesse plays the violin as part of the Band from TV, alongside several TV stars including Greg Grunberg, James Denton and fellow House star, Hugh Laurie.
- He was roommates with actor James McAvoy while he lived in London.
- Jesse still plays the violin, guitar and the piano.
- Jesse and his House co-star Jennifer Morrison called off their engagement on August 15, 2007. They had been engaged since January 2006 when Jesse proposed at the Eiffel Tower in Paris.
- He was born at St Georges Hospital in Kew, Melbourne.
- Jesse was chosen as one of People Magazine's annual 100 Most Beautiful People in the World, in May 2007.
- Since Jesse's father and brothers are all doctors, when they watch House, they always try to diagnose the medical problem in the show and look for medical slip-ups in the dialogue.
- Jesse has blue/green eyes
- Jesse appeared in the 2001 film Winning London with Mary-Kate and Ashley Olsen. He played the character Lord James Browning Jr. and had to put on an English accent for the role
- In 2002, Jesse played the role of Fritz Robinson in the TV movie, Stranded. Stranded was a movie version of the book, The Swiss Family Robinson.
- Jesse is listed as one of "T.V's Sexiest Men" for for 2006.
- Just like his characters Billy Kennedy (Neighbours) and Robert Chase (House M.D) his real life father is a doctor.
- Jesse is soon returning to Australia to make a cameo performance on Neighbours as Billy Kennedy. He previously returned for a guest spot on the show’s 20th anniversary episode in 2005.
- Jesse would like to see his character Chase do a one liner.
- Jesse will be joining his House co-star Jennifer Morrison in the independent movie Flourish.
- He was nominated for the 1999 Silver Logie in the "Most Popular Actor" category.
- Jesse's favourite band is Presidents of the United States of America.
- He was offered a place to study medicine at Melbourne University but he deferred it to pursue a career in acting.
- Jesse's favorite food is chicken.
- His favorite TV show is The X-Files.
- He can speak French.
- He used to have his belly button pierced with a garnet.
- His hobbies include Australian football, running, rock climbing, surfing, and music.
- His first role was as the understudy for the role of Louis in "The King and I."
- He is the son of Rodney and Robyn Spencer.
- He is 5' 10˝" (1.79 m) tall.
- His father and all his siblings are doctors.
- He was in "Uptown Girls" with Brittany Murphy and Dakota Fanning.
- He was in "Death In Holy Orders" and had to use a British accent.
- He plays the guitar, the piano, the violin, and the drums.
- Jesse has played the violin since the age of 10.
- Jesse was in the Australian boys choir.
- Jesse has two older brothers and a younger sister.
- Jesse is Australian but in certain movies puts on a English accent.
- Jesse Spencer: (on Jennifer Morrison) Jennifer boosted my confidence and made me more like the person I want to be.
- Jesse Spencer: Mum decided that I could sing a bit, so she put me in a choir, which I hated and it was just a nightmare. I was a rebellious sort of choirboy.
- Jesse Spencer: I'm from Melbourne - it's a city of about 3 million - but when you're growing up in a place like that and you think it's quite a big city, and then you travel around and you go, 'Actually... no.' So when I go back now, Melbourne feels like a country town. My mum will be in like 15 cars of traffic and she'll be complaining. And I'm like, 'That's not traffic, I'm sorry!'
- Jesse Spencer: I'm the black sheep of the family.
- Jesse Spencer: I'm glad I'm back to being a nobody.
- Jesse Spencer: I started off with violin, then I started learning guitar, then I went to piano. But I self-taught piano just because I enjoyed it. I've always really enjoyed music. I haven't played much the last 4 years because I've been traveling around, so when I got his role [Neal in Uptown Girls], I had to start playing the guitar again.
- Jesse Spencer: I always find music guys writing about love. Think of something else for a change. I'm sorry, but it's been done, and it does work and it's good and all that, but I think something else would be nice. I tend not to write lyrics, cause I'm a bad lyricist. I sort of write the music, and I can orchestrate the whole thing, but the words, [singing] 'I woke up this morning...' Awful stuff.
- Jesse Spencer: Like Billy [his character in Neighbours], my dad is a GP and my two eldest brothers are too. If I wasn't acting I would have definitely gone into medicine, too. It's totally fascinating.
- Jesse Spencer: It's tough in this industry - it doesn't matter whether one is auditioning for an advertisement or for a role in theatre or television - you just learn to take the hundreds of knockbacks! All these people are looking for a certain "look" for each job - the right age, height, hair type, size etc before they even consider any abilities - you learn not to get optimistic or disappointed!